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Autoimmune diseases such as systemic lupus erythematosus (SLE) display a strong female bias. Although sex hormones have been associated with protecting males from autoimmunity, the molecular mechanisms are incompletely understood. Here we report that androgen receptor (AR) expressed in T cells regulates genes involved in T cell activation directly, or indirectly via controlling other transcription factors. T cell-specific deletion of AR in mice leads to T cell activation and enhanced autoimmunity in male mice. Mechanistically, Ptpn22, a phosphatase and negative regulator of T cell receptor signaling, is downregulated in AR-deficient T cells. Moreover, a conserved androgen-response element is found in the regulatory region of Ptpn22 gene, and the mutation of this transcription element in non-obese diabetic mice increases the incidence of spontaneous and inducible diabetes in male mice. Lastly, Ptpn22 deficiency increases the disease severity of male mice in a mouse model of SLE. Our results thus implicate AR-regulated genes such as PTPN22 as potential therapeutic targets for autoimmune diseases.

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The COVID-19 pandemic disproportionately affected Native American people and communities across the United States. Despite unequal losses during the pandemic, Native Americans have high vaccination rates. We provide insight into perspectives of COVID-19 and vaccinations through in-depth interviews with Native Americans. Through this research, we provide a holistic view of how Native Americans perceive vaccines by pairing Indigenous perspectives of risk and the Health Belief Model. We discuss the importance of tribal sovereignty in developing health communication strategies, and the need for messaging that is trusted and culturally appropriate.

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H2-O (human HLA-DO) is a relatively conserved nonclassical MHC class II (MHCII)-like molecule. H2-O interaction with human HLA-DM edits the repertoire of peptides presented to TCRs by MHCII. It was long hypothesized that human HLA-DM inhibition by H2-O provides protection from autoimmunity by preventing binding of the high-affinity self-peptides to MHCII. The available evidence supporting this hypothesis, however, was inconclusive. A possibility still remained that the effect of H2-O deficiency on autoimmunity could be better revealed by using H2-O-deficient mice that were already genetically predisposed to autoimmunity. In this study, we generated and used autoimmunity-prone mouse models for systemic lupus erythematosus and organ-specific autoimmunity (type 1 diabetes and multiple sclerosis) to definitively test whether H2-O prevents autoimmune pathology. Whereas our data failed to support any significance of H2-O in protection from autoimmunity, we found that it was critical for controlling a γ-herpesvirus, MHV68. Thus, we propose that H2-O editing of the MHCII peptide repertoire may have evolved as a safeguard against specific highly prevalent viral pathogens.

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African American, European American, Mexican American, and Native American adolescents (N = 270) described how they felt and appraised their own actions in response to a peer's victimization. Analyses compared times they had calmed victim emotions, amplified anger, avenged, and resolved conflicts peacefully. Adolescents felt prouder, more helpful, more like a good friend, and expected more peer approval after calming and resolving than after amplifying anger or avenging peers. They also felt less guilt and shame after calming and resolving. Avenging elicited more positive self-evaluation than amplifying. Epistemic network analyses explored links between self-evaluative and other emotions. Pride was linked to relief after efforts to calm or resolve. Third-party revenge reflected its antisocial and prosocial nature with connections between pride, relief, anger, and guilt.

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Peer victimization is predictive of serious problems in adjustment, especially among children who are both victimized and aggressive. This study investigated how different types of aggression contribute to later victimization. Specifically, we examined prospective relationships between the types of aggression that children perpetrated and the types that they experienced at the hands of others. Trained observers coded schoolyard behavior of 553 children in grades 3-6 during the initial year of a bullying intervention program. Both observed aggression and victimization were specified by form (direct, indirect) and function (proactive, reactive). Total hourly rates of victimization were highest in the upper grades. Direct-reactive aggression uniquely predicted increases in victimization, while direct-proactive aggression predicted decreases, particularly in direct-proactive victimization. Indirect-proactive aggression (e.g., derogatory gossip) predicted increases in indirect-proactive victimization only in the control group. Indirect-reactive aggression and victimization occurred too rarely to detect change. Aggression-victimization relationships did not differ for boys and girls. Discussion considers why children might risk direct reactive aggression in the face of increased victimization. Different sequelae for different forms and functions of aggression highlight the need to resolve theoretical ambiguities in defining proactive and reactive aggression.

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