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Connecting the innate and adaptive immune responses in mouse choroidal neovascularization via the anaphylatoxin C5a and γδT-cells.
Coughlin, Beth; Schnabolk, Gloriane; Joseph, Kusumam; Raikwar, Himanshu; Kunchithapautham, Kannan; Johnson, Krista; Moore, Kristi; Wang, Yi; Rohrer, Bärbel.
Afiliación
  • Coughlin B; Department of Ophthalmology, Medical University of South Carolina, Charleston, SC 29425, USA.
  • Schnabolk G; Research Service, Ralph H. Johnson VA Medical Center, Charleston, SC 29401, USA.
  • Joseph K; Department of Ophthalmology, Medical University of South Carolina, Charleston, SC 29425, USA.
  • Raikwar H; Department of Ophthalmology, Medical University of South Carolina, Charleston, SC 29425, USA.
  • Kunchithapautham K; Department of Ophthalmology, Medical University of South Carolina, Charleston, SC 29425, USA.
  • Johnson K; Alexion Pharmaceuticals, 352 Knotter Drive, Cheshire CT 06410, USA.
  • Moore K; Alexion Pharmaceuticals, 352 Knotter Drive, Cheshire CT 06410, USA.
  • Wang Y; Alexion Pharmaceuticals, 352 Knotter Drive, Cheshire CT 06410, USA.
  • Rohrer B; Department of Ophthalmology, Medical University of South Carolina, Charleston, SC 29425, USA.
Sci Rep ; 6: 23794, 2016 Mar 31.
Article en En | MEDLINE | ID: mdl-27029558
Neovascular age-related macular degeneration (AMD) is characterized by choroidal neovascularization (CNV). An overactive complement system is associated with AMD pathogenesis, and serum pro-inflammatory cytokines, including IL-17, are elevated in AMD patients. IL-17 is produced by complement C5a-receptor-expressing T-cells. In murine CNV, infiltrating γδT- rather than Th17-cells produce the IL-17 measurable in lesioned eyes. Here we asked whether C5a generated locally in response to CNV recruits IL-17-producing T-cells to the eye. CNV lesions were generated using laser photocoagulation and quantified by imaging; T-lymphocytes were characterized by QRT-PCR. CNV resulted in an increase in splenic IL-17-producing γδT- and Th17-cells; yet in the CNV eye, only elevated levels of γδT-cells were observed. Systemic administration of anti-C5- or anti-C5a-blocking antibodies blunted the CNV-induced production of splenic Th17- and γδT-cells, reduced CNV size and eliminated ocular γδT-cell infiltration. In ARPE-19 cell monolayers, IL-17 triggered a pro-inflammatory state; and splenocyte proliferation was elevated in response to ocular proteins. Thus, we demonstrated that CNV lesions trigger a systemic immune response, augmenting local ocular inflammation via the infiltration of IL-17-producing γδT-cells, which are presumably recruited to the eye in a C5a-dependent manner. Understanding the complexity of complement-mediated pathological mechanisms will aid in the development of an AMD treatment.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Complemento C5a / Coroides / Receptores de Antígenos de Linfocitos T gamma-delta / Linfocitos T CD8-positivos / Neovascularización Coroidal / Células Th17 Tipo de estudio: Etiology_studies Límite: Animals / Humans Idioma: En Revista: Sci Rep Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Complemento C5a / Coroides / Receptores de Antígenos de Linfocitos T gamma-delta / Linfocitos T CD8-positivos / Neovascularización Coroidal / Células Th17 Tipo de estudio: Etiology_studies Límite: Animals / Humans Idioma: En Revista: Sci Rep Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido