NLRP1 acts as a negative regulator of Th17 cell programming in mice and humans with autoimmune diabetes
| Autor: | Maria C Foss-Freitas, Jefferson A. Leite, Jefferson Elias-Oliveira, Rita C. Tostes, Josiane F. Silva, Alessandra Pontillo, Frederico R. C. Costa, Diane M. Rassi, Niels Olsen Saraiva Câmara, Jhefferson Barbosa Guimaraes, João Santana da Silva, Daniela Carlos |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Male endocrine system diseases Cellular differentiation NLR Proteins Biology Peripheral blood mononuclear cell Pyrin domain General Biochemistry Genetics and Molecular Biology Autoimmune Diseases Diabetes Mellitus Experimental 03 medical and health sciences Mice 0302 clinical medicine Immune system Downregulation and upregulation Mice Inbred NOD medicine Animals Humans STAT3 Streptozotocin Rats 030104 developmental biology Diabetes Mellitus Type 1 INTERLEUCINAS Cancer research biology.protein Th17 Cells Interleukin 17 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| Popis: | Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of pancreatic β 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. |
| Databáze: | OpenAIRE |
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