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

Author(s):Show less -

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

• Document type: Journal article
• Source: CELL REPORTS; v. 35, n. 8, p. 15-pg., 2021-05-25.

Abstract

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)

• FAPESP's process: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases
• Grantee: Fernando de Queiroz Cunha
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 12/10395-0 - Role of NLRs receptors in immunoregulation mechanisms of the type 1 and 2 diabetes: identification of potential therapeutic targets
• Grantee: Daniela Carlos Sartori
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 18/14815-0 - Evaluation of the intestinal microbioma profile and of the therapeutic potential of intervention strategies in the immunopathogeny of type 1 and 2 Diabetes
• Grantee: Daniela Carlos Sartori
• Support Opportunities: Research Grants - Young Investigators Grants - Phase 2