IL-17 metabolically reprograms activated fibroblastic reticular cells for proliferation and survival

Autor: Natalie Rittenhouse, Shankar Revu, Saikat Majumder, Fang Du, Sarah L. Gaffen, Ashley V. Menk, Ulrich Siebenlist, Timothy W. Hand, Chetan V. Jawale, Dongwen Wu, Mandy J. McGeachy, Itay Raphael, Nilesh Amatya, Amanda C. Poholek, Greg M. Delgoffe, Saran Kupul, Partha S. Biswas, Amrita Bhattacharjee
Rok vydání: 2019
Předmět:
Zdroj: Nature Immunology. 20:534-545
ISSN: 1529-2916
1529-2908
Popis: 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 IκBζ 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. Fibroblastic reticular cells support lymph-node function and adaptive immunity. McGeachy and colleagues show that the cytokine IL-17 is needed to trigger metabolic changes required for the proliferation and survival of these cells in reactive lymph nodes.
Databáze: OpenAIRE
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