| First Author | Jain A | Year | 2020 |
| Journal | Nat Immunol | Volume | 21 |
| Issue | 1 | Pages | 65-74 |
| PubMed ID | 31848486 | Mgi Jnum | J:306894 |
| Mgi Id | MGI:6706715 | Doi | 10.1038/s41590-019-0559-y |
| Citation | Jain A, et al. (2020) T cells instruct myeloid cells to produce inflammasome-independent IL-1beta and cause autoimmunity. Nat Immunol 21(1):65-74 |
| abstractText | The cytokine interleukin (IL)-1beta is a key mediator of antimicrobial immunity as well as autoimmune inflammation. Production of IL-1beta requires transcription by innate immune receptor signaling and maturational cleavage by inflammasomes. Whether this mechanism applies to IL-1beta production seen in T cell-driven autoimmune diseases remains unclear. Here, we describe an inflammasome-independent pathway of IL-1beta production that was triggered upon cognate interactions between effector CD4(+) T cells and mononuclear phagocytes (MPs). The cytokine TNF produced by activated CD4(+) T cells engaged its receptor TNFR on MPs, leading to pro-IL-1beta synthesis. Membrane-bound FasL, expressed by CD4(+) T cells, activated death receptor Fas signaling in MPs, resulting in caspase-8-dependent pro-IL-1beta cleavage. The T cell-instructed IL-1beta resulted in systemic inflammation, whereas absence of TNFR or Fas signaling protected mice from CD4(+) T cell-driven autoimmunity. The TNFR-Fas-caspase-8-dependent pathway provides a mechanistic explanation for IL-1beta production and its consequences in CD4(+) T cell-driven autoimmune pathology. |
