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As terahertz (THz) technology advances, the interaction between THz radiation and the living body, particularly its effects on the immune system, has attracted extensive attention but remains poorly understood. This study firstly elucidated that exposure to 3 THz-FEL radiation markedly suppressed contact hypersensitivity reactions in mice induced by DNFB, as evidenced by a reduction in ear thickness and a discernible recovery in the Th1/Th2 cell balance. 3 THz irradiation led to cellular stress in the irradiated skin locale, increasing the levels of IL-4 and IL-10 and modulating the activity and migration of dendritic cells and mast cells. Furthermore, THz irradiation precipitated a rapid alteration in the skin lipidome, altering several categories of bioactive lipids. These findings offer new insights into the immunomodulatory effects of THz radiation on living organisms and the potential underlying mechanisms, with implications for the development of therapeutic approaches in managing skin allergic diseases.
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Interleucina-4 , Mastocitos , Piel , Radiación Terahertz , Animales , Ratones , Mastocitos/efectos de la radiación , Mastocitos/inmunología , Piel/efectos de la radiación , Interleucina-4/metabolismo , Células Dendríticas/efectos de la radiación , Células Dendríticas/inmunología , Interleucina-10/metabolismo , Dermatitis por Contacto/inmunología , Dermatitis por Contacto/etiología , Ratones Endogámicos BALB C , Dinitrofluorobenceno , Femenino , Células Th2/efectos de la radiación , Células Th2/inmunología , Células TH1/efectos de la radiación , Células TH1/inmunologíaRESUMEN
Global amphibian declines are compounded by deadly disease outbreaks caused by the chytrid fungus, Batrachochytrium dendrobatidis (Bd). Much has been learned about the roles of amphibian skin-produced antimicrobial components and microbiomes in controlling Bd, yet almost nothing is known about the roles of skin-resident immune cells in anti-Bd defenses. Mammalian mast cells reside within and serve as key immune sentinels in barrier tissues like skin. Accordingly, we investigated the roles of Xenopus laevis frog mast cells during Bd infections. Our findings indicate that enrichment of X. laevis skin mast cells confers anti-Bd protection and ameliorates the inflammation-associated skin damage caused by Bd infection. This includes a significant reduction in infiltration of Bd-infected skin by neutrophils, promoting mucin content within cutaneous mucus glands, and preventing Bd-mediated changes to skin microbiomes. Mammalian mast cells are known for their production of the pleiotropic interleukin-4 (IL4) cytokine and our findings suggest that the X. laevis IL4 plays a key role in manifesting the effects seen following cutaneous mast cell enrichment. Together, this work underscores the importance of amphibian skin-resident immune cells in anti-Bd defenses and illuminates a novel avenue for investigating amphibian host-chytrid pathogen interactions.
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Batrachochytrium , Mastocitos , Piel , Xenopus laevis , Animales , Mastocitos/inmunología , Mastocitos/microbiología , Mastocitos/metabolismo , Xenopus laevis/microbiología , Xenopus laevis/inmunología , Piel/microbiología , Piel/inmunología , Micosis/inmunología , Micosis/veterinaria , Micosis/microbiología , MicrobiotaRESUMEN
Dengue virus (DENV) poses a global health threat, affecting millions individuals annually with no specific therapy and limited vaccines. Mosquitoes, mainly Aedes aegypti and Aedes albopictus worldwide, transmit DENV through their saliva during blood meals. In this study, we aimed to understand how Aedes mosquito saliva modulate skin immune responses during DENV infection in individuals living in mosquito-endemic regions. To accomplish this, we dissociated skin cells from Cambodian volunteers and incubated them with salivary gland extract (SGE) from three different mosquito strains: Ae. aegypti USDA strain, Ae. aegypti and Ae. albopictus wild type (WT) in the presence/absence of DENV. We observed notable alterations in skin immune cell phenotypes subsequent to exposure to Aedes salivary gland extract (SGE). Specifically, exposure lead to an increase in the frequency of macrophages expressing chemokine receptor CCR2, and neutrophils expressing CD69. Additionally, we noted a substantial increase in the percentage of macrophages that became infected with DENV in the presence of Aedes SGE. Differences in cellular responses were observed when Aedes SGE of three distinct mosquito strains were compared. Our findings deepen the understanding of mosquito saliva's role in DENV infection and skin immune responses in individuals regularly exposed to mosquito bites. This study provides insights into skin immune cell dynamics that could guide strategies to mitigate DENV transmission and other arbovirus diseases.
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BACKGROUND: The skin barrier is vital for protection against environmental threats including insults caused by skin-resident microbes. Dysregulation of this barrier is a hallmark of atopic dermatitis (AD) and ichthyosis, with variable consequences for host immune control of colonizing commensals and opportunistic pathogens. While Malassezia is the most abundant commensal fungus of the skin, little is known about the host control of this fungus in inflammatory skin diseases. METHODS: In this experimental study, MC903-treated mice were colonized with Malassezia spp. to assess the host-fungal interactions in atopic dermatitis. Additional murine models of AD and ichthyosis, including tape stripping, K5-Nrf2 overexpression and flaky tail mice, were employed to confirm and expand the findings. Skin fungal counts were enumerated. High parameter flow cytometry was used to characterize the antifungal response in the AD-like skin. Structural and functional alterations in the skin barrier were determined by histology and transcriptomics of bulk skin. Finally, differential expression of metabolic genes in Malassezia in atopic and control skin was quantified. RESULTS: Malassezia grows excessively in AD-like skin. Fungal overgrowth could, however, not be explained by the altered immune status of the atopic skin. Instead, we found that by upregulating key metabolic genes in the altered cutaneous niche, Malassezia acquired enhanced fitness to efficiently colonise the impaired skin barrier. CONCLUSIONS: This study provides evidence that structural and metabolic changes in the dysfunctional epidermal barrier environment provide increased accessibility and an altered lipid profile, to which the lipid-dependent yeast adapts for enhanced nutrient assimilation. Our findings reveal fundamental insights into the implication of the mycobiota in the pathogenesis of common skin barrier disorders.
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Dermatitis Atópica , Modelos Animales de Enfermedad , Malassezia , Piel , Animales , Malassezia/inmunología , Ratones , Dermatitis Atópica/microbiología , Dermatitis Atópica/inmunología , Piel/microbiología , Piel/inmunología , Epidermis/microbiología , Epidermis/inmunología , Epidermis/metabolismo , Susceptibilidad a Enfermedades , Hipersensibilidad/inmunología , Hipersensibilidad/microbiología , FemeninoRESUMEN
The skin presents a multifaceted microbiome, a balanced coexistence of bacteria, fungi, and viruses. These resident microorganisms are fundamental in upholding skin health by both countering detrimental pathogens and working in tandem with the skin's immunity. Disruptions in this balance, known as dysbiosis, can lead to disorders like psoriasis and atopic dermatitis. Central to the skin's defense system are mast cells. These are strategically positioned within the skin layers, primed for rapid response to any potential foreign threats. Recent investigations have started to unravel the complex interplay between these mast cells and the diverse entities within the skin's microbiome. This relationship, especially during times of both balance and imbalance, is proving to be more integral to skin health than previously recognized. In this review, we illuminate the latest findings on the ties between mast cells and commensal skin microorganisms, shedding light on their combined effects on skin health and maladies.
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Dermatitis Atópica , Microbiota , Psoriasis , Humanos , Mastocitos , Piel , Psoriasis/microbiologíaRESUMEN
The continual emergence of SARS-CoV-2 variants threatens to compromise the effectiveness of worldwide vaccination programs, and highlights the need for complementary strategies for a sustainable containment plan. An effective approach is to mobilize the body's own antimicrobial peptides (AMPs), to combat SARS-CoV-2 infection and propagation. We have found that human cathelicidin (LL37), an AMP found at epithelial barriers as well as in various bodily fluids, has the capacity to neutralise multiple strains of SARS-CoV-2. Biophysical and computational studies indicate that LL37's mechanism of action is through the disruption of the viral membrane. This antiviral activity of LL37 is enhanced by the hydrotropic action of niacinamide, which may increase the bioavailability of the AMP. Interestingly, we observed an inverse correlation between LL37 levels and disease severity of COVID-19 positive patients, suggesting enhancement of AMP response as a potential therapeutic avenue to mitigate disease severity. The combination of niacinamide and LL37 is a potent antiviral formulation that targets viral membranes of various variants and can be an effective strategy to overcome vaccine escape.
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COVID-19 , Catelicidinas , Humanos , Catelicidinas/farmacología , SARS-CoV-2 , Péptidos Catiónicos Antimicrobianos/farmacología , Niacinamida , AntiviralesRESUMEN
Allergic contact dermatitis (ACD) is an occupation-dependent skin disease that afflicts humans with recurrent, non-specific episodes. Telocyte (TC) is a novel interstitial cell discovered in recent years and, together with fibroblasts, constitutes the predominant interstitial cell population in the skin. The purpose of this study was to investigate the morphodynamic changes of interstitial cells, especially TCs, in the skin during the development and treatment of ACD by histological and microscopic scientific methods. Hematoxylin-eosin staining, Masson staining, immunohistochemistry (IHC), immunofluorescence (IF), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) were used to track morphodynamic changes in interstitial cells during the development and treatment in the ACD-involved skin induced by 2,4-dinitrochlorobenzene (DNCB). The results demonstrated that TCs were mainly present around dermal collagen fibers, perivascular (except dermal papillary vascular loop), and skin appendages, which expressed CD34+, Vimentin+, PDGFR-α+, and α-SMA-. The absence of TCs during ACD development and after ACD recovery causes dermal interstitial cell dysregulation. The special anatomical relationships between TCs, immune cells, and follicular stem cells were also revealed, suggesting their potential dermatitis-regulating function. In a nutshell, our results provide morphodynamic evidence for the process of ACD development and recovery and offer potential cytological ideas for ACD treatment.
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Dermatitis Alérgica por Contacto , Células Intersticiales de Cajal , Telocitos , Humanos , Telocitos/ultraestructura , Piel/patología , Dermatitis Alérgica por Contacto/patología , InmunohistoquímicaRESUMEN
Tissue-resident memory CD8+ T cells (TRM) reside at sites of previous infection, providing protection against reinfection with the same pathogen. In the skin, TRM patrol the epidermis, where keratinocytes are the entry site for many viral infections. Epidermal TRM react rapidly to cognate antigen encounter with the secretion of cytokines and differentiation into cytotoxic effector cells, constituting a first line of defense against skin reinfection. Despite the important protective role of skin TRM, it has remained unclear, whether their reactivation requires a professional antigen-presenting cell (APC). We show here, using a model system that allows antigen targeting selectively to keratinocytes in a defined area of the skin, that limited antigen expression by keratinocytes results in rapid, antigen-specific reactivation of skin TRM. Our data identify epidermal Langerhans cells that cross-present keratinocyte-derived antigens, as the professional APC indispensable for the early reactivation of TRM in the epidermal layer of the skin.
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Linfocitos T CD8-positivos , Células de Langerhans , Humanos , Células T de Memoria , Reinfección/metabolismo , Epidermis , Antígenos , Memoria InmunológicaRESUMEN
Ticks can transmit a variety of human pathogens, including intracellular and extracellular bacteria, viruses, and protozoan parasites. Historically, their saliva has been of immense interest due to its anticoagulant, anti-inflammatory, and anesthetic properties. Only recently, it was discovered that tick saliva contains extracellular vesicles (EVs). Briefly, it has been observed that proteins associated with EVs are important for multiple tick-borne intracellular microbial lifestyles. The impact of tick EVs on viral and intracellular bacterial pathogen transmission from the tick to the mammalian host has been shown experimentally. Additionally, tick EVs interact with the mammalian skin immune system at the bite site. The interplay between tick EVs, the transmission of pathogens, and the host skin immune system affords opportunities for future research.
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Vesículas Extracelulares , Piel , Humanos , Animales , Saliva , MamíferosRESUMEN
The skin is the body's largest organ. It serves as a barrier to pathogen entry and the first site of immune defense. In the event of a skin injury, a cascade of events including inflammation, new tissue formation and tissue remodeling contributes to wound repair. Skin-resident and recruited immune cells work together with non-immune cells to clear invading pathogens and debris, and guide the regeneration of damaged host tissues. Disruption to the wound repair process can lead to chronic inflammation and non-healing wounds. This, in turn, can promote skin tumorigenesis. Tumors appropriate the wound healing response as a way of enhancing their survival and growth. Here we review the role of resident and skin-infiltrating immune cells in wound repair and discuss their functions in regulating both inflammation and development of skin cancers.
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Piel , Cicatrización de Heridas , Humanos , Piel/patología , Inflamación , Carcinogénesis/patologíaRESUMEN
Human CD1a is a non-polymorphic glycoprotein that presents lipid antigens to T cells. The most obvious role of CD1a is associated with its expression on Langerhans cells in epidermis, where it is involved in responses to pathogens. Antigen-specific T cells are believed to co-recognise CD1a presenting bacterial antigens such as species of lipopeptides from Mycobacterium tuberculosis. Further, human skin contains large amount of endogenous lipids that can activate distinct subsets of CD1a-restricted autoreactive T cells, mostly belonging to the αß lineage, which are abundant in human blood and skin and are important for skin homeostasis in healthy individuals. CD1a and CD1a-restricted T cells have been linked to certain autoimmune conditions such as psoriasis, atopic dermatitis and contact hypersensitivity becoming a potential candidate for clinical interventions. A significant progress has been made in the last twenty years towards our understanding of the molecular processes that orchestrate CD1a-lipid binding, antigen presentation and mechanism of CD1a recognition by αß and γδ T cells. This review summarises the recent developments within the field of CD1a-mediated immunity from a molecular perspective.
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Dermatitis Atópica , Piel , Humanos , Presentación de Antígeno , Antígenos CD1 , Células de Langerhans , Lípidos , Linfocitos TRESUMEN
Malaria is caused by Plasmodium protozoa that are transmitted by anopheline mosquitoes. Plasmodium sporozoites are released with saliva when an infected female mosquito takes a blood meal on a vertebrate host. Sporozoites deposited into the skin must enter a blood vessel to start their journey towards the liver. After migration out of the mosquito, sporozoites are associated with, or in proximity to, many components of vector saliva in the skin. Recent work has elucidated how Anopheles saliva, and components of saliva, can influence host-pathogen interactions during the early stage of Plasmodium infection in the skin. Here, we discuss how components of Anopheles saliva can modulate local host responses and affect Plasmodium infectivity. We hypothesize that therapeutic strategies targeting mosquito salivary proteins can play a role in controlling malaria and other vector-borne diseases.
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Anopheles , Malaria , Humanos , Animales , Femenino , Anopheles/parasitología , Anopheles/fisiología , Saliva , Mosquitos Vectores/parasitología , EsporozoítosRESUMEN
Epigenetics has been well understood for its role in cell development; however, it is now known to regulate many processes involved in immune cell activation in a variety of cells. The skin maintains homeostasis via crosstalk between immune and non-immune cells. Disruption of normal epigenetic regulation in these cells may alter the transcription of immune-regulatory factors and affect the immunological balance in the skin. This review summarizes recent evidence for the epigenetic regulation of skin immunity. Much of what is known about epigenetic involvement in skin immunity is associated with DNA methylation. This review focuses on epigenetic regulation of histone modification and chromatin remodeling and describes their role in the transcriptional regulation of immune-regulatory factors. While much is still unknown regarding the regulation of skin immunity via histone modification or chromatin remodeling, these processes may underlie the pathogenesis of chronic cutaneous immune disorders.
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Metilación de ADN , Epigénesis Genética , Regulación de la Expresión Génica , Piel , Ensamble y Desensamble de CromatinaRESUMEN
Fungi represent an integral part of the skin microbiota. Their complex interaction network with the host shapes protective immunity during homeostasis. If host defences are breached, skin-resident fungi including Malassezia and Candida, and environmental fungi such as dermatophytes can cause cutaneous infections. In addition, fungi are associated with diverse non-infectious skin disorders. Despite their multiple roles in health and disease, fungi remain elusive and understudied, and the mechanisms underlying the emergence of pathological conditions linked to fungi are largely unclear. The identification of IL-17 as an important antifungal effector mechanism represents a milestone for understanding homeostatic antifungal immunity. At the same time, host-adverse, disease-promoting roles of IL-17 have been delineated, as in psoriasis. Fungal dysbiosis represents another feature of many pathological skin conditions with an unknown causal link of intra- and interkingdom interactions to disease pathogenesis. The emergence of new fungal pathogens such as Candida auris highlights the need for more research into fungal immunology to understand how antifungal responses shape health and diseases. Recent technological advances for genetically manipulating fungi to target immunomodulatory fungal determinants, multi-omics approaches for studying immune cells in the human skin, and novel experimental models open up a promising future for skin fungal immunity.
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Malassezia , Microbiota , Humanos , Interleucina-17 , Antifúngicos , Piel , Hongos/fisiologíaRESUMEN
Arthritogenic alphaviruses are mosquito-borne arboviruses that include several re-emerging human pathogens, including the chikungunya (CHIKV), Ross River (RRV), Mayaro (MAYV), and o'nyong-nyong (ONNV) virus. Arboviruses are transmitted via a mosquito bite to the skin. Herein, we describe intradermal RRV infection in a mouse model that replicates the arthritis and myositis seen in humans with Ross River virus disease (RRVD). We show that skin infection with RRV results in the recruitment of inflammatory monocytes and neutrophils, which together with dendritic cells migrate to draining lymph nodes (LN) of the skin. Neutrophils and monocytes are productively infected and traffic virus from the skin to LN. We show that viral envelope N-linked glycosylation is a key determinant of skin immune responses and disease severity. RRV grown in mammalian cells elicited robust early antiviral responses in the skin, while RRV grown in mosquito cells stimulated poorer early antiviral responses. We used glycan mass spectrometry to characterize the glycan profile of mosquito and mammalian cell-derived RRV, showing deglycosylation of the RRV E2 glycoprotein is associated with curtailed skin immune responses and reduced disease following intradermal infection. Altogether, our findings demonstrate skin infection with an arthritogenic alphavirus leads to musculoskeletal disease and envelope glycoprotein glycosylation shapes disease outcome. IMPORTANCE Arthritogenic alphaviruses are transmitted via mosquito bites through the skin, potentially causing debilitating diseases. Our understanding of how viral infection starts in the skin and how virus systemically disseminates to cause disease remains limited. Intradermal arbovirus infection described herein results in musculoskeletal pathology, which is dependent on viral envelope N-linked glycosylation. As such, intradermal infection route provides new insights into how arboviruses cause disease and could be extended to future investigations of skin immune responses following infection with other re-emerging arboviruses.
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Infecciones por Alphavirus , Artritis , Miositis , Polisacáridos , Virus del Río Ross , Piel , Infecciones por Alphavirus/complicaciones , Infecciones por Alphavirus/inmunología , Animales , Antivirales/inmunología , Artritis/complicaciones , Artritis/inmunología , Culicidae/virología , Células Dendríticas , Modelos Animales de Enfermedad , Glicosilación , Humanos , Espectrometría de Masas , Ratones , Monocitos , Miositis/complicaciones , Miositis/inmunología , Neutrófilos , Polisacáridos/química , Polisacáridos/inmunología , Virus del Río Ross/inmunología , Piel/inmunología , Piel/virología , Proteínas del Envoltorio Viral/química , Proteínas del Envoltorio Viral/inmunologíaRESUMEN
Resident microbes in skin and gut predominantly impact local immune cell function during homeostasis. However, colitis-associated neutrophilic skin disorders suggest possible breakdown of this compartmentalization with disease. Using a model wherein neonatal skin colonization by Staphylococcus epidermidis facilitates generation of commensal-specific tolerance and CD4+ regulatory T cells (Tregs), we ask whether this response is perturbed by gut inflammation. Chemically induced colitis is accompanied by intestinal expansion of S. epidermidis and reduces gut-draining lymph node (dLN) commensal-specific Tregs. It also results in reduced commensal-specific Tregs in skin and skin-dLNs and increased skin neutrophils. Increased CD4+ circulation between gut and skin dLN suggests that the altered cutaneous response is initiated in the colon, and resistance to colitis-induced effects in Cd4creIl1r1fl/fl mice implicate interleukin (IL)-1 in mediating the altered commensal-specific response. These findings provide mechanistic insight into observed connections between inflammatory skin and intestinal diseases.
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Colitis , Inmunidad , Animales , Colitis/inducido químicamente , Inflamación , Ratones , Piel , Staphylococcus epidermidis , Linfocitos T ReguladoresRESUMEN
The genus Leishmania comprises a wide range of species, some of which are pathogenic to humans and each of which has a different tissue preference, resulting in one of the three clinical forms of human leishmaniasis: visceral, cutaneous, or mucocutaneous. Although, all pathogenic species are deposited intradermally in the mammalian host upon an infectious sand fly bite, only the viscerotropic strains can leave the skin and reach the internal organs. We assume that Leishmania tissue tropism is not only the result of Leishmania genetic determinism but is also governed by the interaction of the parasite with different vectorial and human host elements. To shed light on these elements and key steps determining the course of the infection, we describe throughout this review the disease's progression from the early stages of infection taking place in the skin to the late stages succeeding in the parasite's visceral dissemination. Hence, we address the question of Leishmania tropism, through providing relevant hypotheses and answers gathered from the literature.
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Leishmania , Leishmaniasis Cutánea , Leishmaniasis Visceral , Animales , Leishmania/genética , Leishmaniasis Cutánea/parasitología , Leishmaniasis Visceral/parasitología , Mamíferos , Piel/patología , TropismoRESUMEN
The dermal microvascular unit (DMU) is a perivascular functional unit in the dermis. It is composed of microvascular and capillary lymphatics surrounded by immune cells. In this study, jet needle-free injection system was used to injected biocompatible carbon nanoparticles into the cervical skin of domestic pigs (Sus scrofa domestica) and assessed the morphological distribution of DMUs by hematoxylin erythrosine staining, immunohistochemistry (IHC), and transmission electron microscopy (TEM), and TEM was also used to observe the ultrastructural changes of DMUs after jet needle-free injection. Following our study, we identified DMUs in the dermis stratum papillare and similar structures in the dermis stratum reticulare, but the aggregation of CD68+ and CD1a+ cells in the dermis stratum papillare of DMUs by IHC confirmed that DMUs act as reservoirs of dermal immune cells, while similar structures in the dermis stratum reticulare should not be considered as DMUs. Ultrastructure of DMUs was revealed by TEM. Marvelous changes were found following xenobiotics attack, including the rearrangement of endothelial cells and pericytes, and the reactivity of immune cells. Novel interstitial cell telocyte (TC) was also identified around the microvasculature, which may have been previously known as the veil cell. Our results successfully identified the distribution of DMUs in the skin of domestic pigs, which might act as reservoirs of immune cells in the skin and play a role in immune surveillance and immune defense.
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A variety of non-filtering agents have been introduced to enhance sunscreen photoprotection. Most of those agents have only weak erythema protective properties but may be valuable and beneficial in supporting protection against other effects of UV radiation, such as photoimmunosuppression, skin aging, and carcinogenesis, as well as photodermatoses. The question arises how to measure and evaluate this efficacy since standard SPF testing is not appropriate. In this perspective, we aim to provide a position statement regarding the actual value of SPF and UVA-PF to measure photoprotection. We argue whether new or additional parameters and scales can be used to better indicate the protection conferred by these products against the detrimental effects of natural/artificial, UV/visible light beyond sunburn, including DNA damage, photoimmunosuppression and pigmentation, and the potential benefits of the addition of other ingredients beyond traditional inorganic and organic filters to existing sunscreens. Also, we debate the overall usefulness of adding novel parameters that measure photoprotection to reach two tiers of users, that is, the general public and the medical community; and how this can be communicated to convey the presence of additional beneficial effects deriving from non-filtering agents, e.g., biological extracts. Finally, we provide a perspective on new challenges stemming from environmental factors, focusing on the role of the skin microbiome and the role of air pollutants and resulting needs for photoprotection.
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Extensive research is underway to discover a safe and effective vehicle to deliver the vaccines at the desired cutaneous site. These efforts majorly comprise the development of a fit-to-purpose vehicle for in-situ intracutaneous vaccine delivery for achieving the systemic cellular and humoral response to combat infectious diseases. Advancements in nanoscience, bioengineering, and skin science provided much support to vaccine adjuvant development. However, the bench-to-bed side translation of vaccines is still unsatisfactory. A skilfully designed vaccine delivery program aiming to translate the product into market use must address safety, efficacy, scaleup, reproducibility, cost of production, self-administrative potential, and regulatory concerns. This review provides deep insights into skin immunization approaches like mucosal vaccines, cellular/molecular immunological responses, and antigen-adjuvant combinations in modulating immunity. Further, the manuscript discusses distinct vaccine delivery systems used to date for engineering skin immunization, including microparticles, nanoparticles, spherical nucleic acids, STAR particles, niosomes, dendrimers, ethosomes, liposomes, and microneedles. The manuscript will interest researchers working towards developing a next-generation fit-to-purpose vehicle for intracutaneous vaccine delivery.