| First Author | Costa FRC | Year | 2021 |
| Journal | Cell Rep | Volume | 35 |
| Issue | 8 | Pages | 109176 |
| PubMed ID | 34038731 | Mgi Jnum | J:324648 |
| Mgi Id | MGI:6717052 | Doi | 10.1016/j.celrep.2021.109176 |
| Citation | Costa FRC, et al. (2021) NLRP1 acts as a negative regulator of Th17 cell programming in mice and humans with autoimmune diabetes. Cell Rep 35(8):109176 |
| abstractText | 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. |
