| First Author | Majumder S | Year | 2019 |
| Journal | Nat Immunol | Volume | 20 |
| Issue | 5 | Pages | 534-545 |
| PubMed ID | 30962593 | Mgi Jnum | J:282323 |
| Mgi Id | MGI:6380946 | Doi | 10.1038/s41590-019-0367-4 |
| Citation | Majumder S, et al. (2019) IL-17 metabolically reprograms activated fibroblastic reticular cells for proliferation and survival. Nat Immunol 20(5):534-545 |
| abstractText | Lymph-node (LN) stromal cell populations expand during the inflammation that accompanies T cell activation. Interleukin-17 (IL-17)-producing helper T cells (TH17 cells) promote inflammation through the induction of cytokines and chemokines in peripheral tissues. We demonstrate a critical requirement for IL-17 in the proliferation of LN and splenic stromal cells, particularly fibroblastic reticular cells (FRCs), during experimental autoimmune encephalomyelitis and colitis. Without signaling via the IL-17 receptor, activated FRCs underwent cell cycle arrest and apoptosis, accompanied by signs of nutrient stress in vivo. IL-17 signaling in FRCs was not required for the development of TH17 cells, but failed FRC proliferation impaired germinal center formation and antigen-specific antibody production. Induction of the transcriptional co-activator IkappaBzeta via IL-17 signaling mediated increased glucose uptake and expression of the gene Cpt1a, encoding CPT1A, a rate-limiting enzyme of mitochondrial fatty acid oxidation. Hence, IL-17 produced by locally differentiating TH17 cells is an important driver of the activation of inflamed LN stromal cells, through metabolic reprogramming required to support proliferation and survival. |
