Interleukin-17A Serves a Priming Role in Autoimmunity by Recruiting IL-1β-Producing Myeloid Cells that Promote Pathogenic T Cells.

Interleukin-17A (IL-17A) is a major mediator of tissue inflammation in many autoimmune diseases. Anti-IL-17A is an effective treatment for psoriasis and is showing promise in clinical trials in multiple sclerosis. In this study, we find that IL-17A-defective mice or mice treated with anti-IL-17A at...

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Detalhes bibliográficos
Autores: McGinley, Aoife M, Sutton, Caroline E, Edwards, Sarah C, Leane, Charlotte M, DeCourcey, Joseph, Teijeiro, Ana, Hamilton, John A, Boon, Louis, Djouder, Nabil, Mills, Kingston H G
Formato: artículo
Fecha de publicación:2020
País:España
Recursos:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/17561
Acesso em linha:http://hdl.handle.net/20.500.12105/17561
Access Level:acceso abierto
Palavra-chave:Animals
Autoantigens
Autoimmunity
Central Nervous System
Encephalomyelitis, Autoimmune, Experimental
Interleukin-17
Interleukin-1beta
Interleukin-23
Intraepithelial Lymphocytes
Mice
Mice, Inbred C57BL
Mice, Knockout
Monocytes
Myeloid Cells
Neutrophils
Th17 Cells
Descrição
Resumo:Interleukin-17A (IL-17A) is a major mediator of tissue inflammation in many autoimmune diseases. Anti-IL-17A is an effective treatment for psoriasis and is showing promise in clinical trials in multiple sclerosis. In this study, we find that IL-17A-defective mice or mice treated with anti-IL-17A at induction of experimental autoimmune encephalomyelitis (EAE) are resistant to disease and have defective priming of IL-17-secreting γδ T (γδT17) cells and Th17 cells. However, T cells from Il17a-/- mice induce EAE in wild-type mice following in vitro culture with autoantigen, IL-1β, and IL-23. Furthermore, treatment with IL-1β or IL-17A at induction of EAE restores disease in Il17a-/- mice. Importantly, mobilization of IL-1β-producing neutrophils and inflammatory monocytes and activation of γδT17 cells is reduced in Il17a-/- mice. Our findings demonstrate that a key function of IL-17A in central nervous system (CNS) autoimmunity is to recruit IL-1β-secreting myeloid cells that prime pathogenic γδT17 and Th17 cells.

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