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Nat Immunol. 2019 May;20(5):534-545. doi: 10.1038/s41590-019-0367-4. Epub 2019 Apr 8.

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

Author information

1
Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
2
Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA, USA.
3
Tumor Microenvironment Center, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA.
4
Immune Activation Section, NIAID, National Institutes of Health, Bethesda, MD, USA.
5
Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA. mandymcgeachy@pitt.edu.

Abstract

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.

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PMID:
30962593
PMCID:
PMC6519710
DOI:
10.1038/s41590-019-0367-4
[Indexed for MEDLINE]
Free PMC Article

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