| First Author | Alvarez-Martinez M | Year | 2024 |
| Journal | Nat Immunol | Volume | 25 |
| Issue | 5 | Pages | 886-901 |
| PubMed ID | 38609547 | Mgi Jnum | J:362417 |
| Mgi Id | MGI:7705461 | Doi | 10.1038/s41590-024-01814-z |
| Citation | Alvarez-Martinez M, et al. (2024) Blimp-1 and c-Maf regulate immune gene networks to protect against distinct pathways of pathobiont-induced colitis. Nat Immunol 25(5):886-901 |
| abstractText | Intestinal immune responses to microbes are controlled by the cytokine IL-10 to avoid immune pathology. Here, we use single-cell RNA sequencing of colon lamina propria leukocytes (LPLs) along with RNA-seq and ATAC-seq of purified CD4(+) T cells to show that the transcription factors Blimp-1 (encoded by Prdm1) and c-Maf co-dominantly regulate Il10 while negatively regulating proinflammatory cytokines in effector T cells. Double-deficient Prdm1(fl/fl)Maf(fl/fl)Cd4(Cre) mice infected with Helicobacter hepaticus developed severe colitis with an increase in T(H)1/NK/ILC1 effector genes in LPLs, while Prdm1(fl/fl)Cd4(Cre) and Maf(fl/fl)Cd4(Cre) mice exhibited moderate pathology and a less-marked type 1 effector response. LPLs from infected Maf(fl/fl)Cd4(Cre) mice had increased type 17 responses with increased Il17a and Il22 expression and an increase in granulocytes and myeloid cell numbers, resulting in increased T cell-myeloid-neutrophil interactions. Genes over-expressed in human inflammatory bowel disease showed differential expression in LPLs from infected mice in the absence of Prdm1 or Maf, revealing potential mechanisms of human disease. |
