NLRP1 acts as a negative regulator of Th17 cell programming in mice and humans with autoimmune diabetes

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Costa, Frederico R. C. ; Leite, Jefferson A. ; Rassi, Diane M. ; da Silva, Josiane F. ; Elias-Oliveira, Jefferson ; Guimaraes, Jhefferson B. ; Foss-Freitas, Maria C. ; Camara, Niels O. S. ; Pontillo, Alessandra ; Tostes, Rita C. ; Silva, Joao S. ; Carlos, Daniela

• Tipo de documento: Artigo Científico
• Fonte: CELL REPORTS; v. 35, n. 8, p. 15-pg., 2021-05-25.

Resumo

Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of pancreatic beta cells, We show here that the protein NOD-like receptor family pyrin domain containing 1 (NLRP1) has a key role in the pathogenesis of mouse and human T1D. More specifically, downregulation of NLRP1 expression occurs during T helper 17 (Th17) differentiation, alongside greater expression of several molecules related to Th17 cell differentiation in a signal transducers and activators of transcription 3 (STAT3)-dependent pathway. These changes lead to a consequent increase in interleukin 17 (IL-17) production within the pancreas and higher incidence of diabetes in streptozotocin (STZ)-injected mice. Finally, in patients with T1D and a SNP (rs12150220) in NLRP1, there is a robust decrease in IL-17 levels in serum and in memory Th17 cells from peripheral blood mononuclear cells. Our results demonstrate that NLRP1 acts as a negative regulator of the Th17 cell polarization program, making it an interesting target for intervention during the early stages of T1D. (AU)

• Processo FAPESP: 13/08216-2 - CPDI - Centro de Pesquisa em Doenças Inflamatórias
• Beneficiário: Fernando de Queiroz Cunha
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 12/10395-0 - Papel dos receptores NLRs nos mecanismos de imunoregulação do diabetes do tipo 1 e 2: identificação de novos alvos terapêuticos
• Beneficiário: Daniela Carlos Sartori
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 18/14815-0 - Estudo do perfil do microbioma intestinal e do potencial terapêutico de estratégias de intervenção na imunopatogenia do Diabetes tipo 1 e 2
• Beneficiário: Daniela Carlos Sartori
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores - Fase 2