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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibody Formation / genetics
  • Antibody Formation / immunology
  • Cell Proliferation*
  • Cell Survival / genetics
  • Cell Survival / immunology
  • Cells, Cultured
  • Colitis / genetics
  • Colitis / immunology
  • Colitis / metabolism
  • Encephalomyelitis, Autoimmune, Experimental / genetics
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Encephalomyelitis, Autoimmune, Experimental / metabolism
  • Fibroblasts / immunology*
  • Fibroblasts / metabolism
  • Interleukin-17 / genetics
  • Interleukin-17 / immunology*
  • Interleukin-17 / metabolism
  • Lymph Nodes / cytology
  • Lymph Nodes / immunology*
  • Lymph Nodes / metabolism
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Receptors, Interleukin-17 / genetics
  • Receptors, Interleukin-17 / immunology
  • Receptors, Interleukin-17 / metabolism
  • Stromal Cells / immunology*
  • Stromal Cells / metabolism
  • Th17 Cells / immunology
  • Th17 Cells / metabolism


  • Interleukin-17
  • Receptors, Interleukin-17