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

被引：90

作者：

Majumder, Saikat ^{[1
]}

Amatya, Nilesh ^{[1
]}

Revu, Shankar ^{[1
]}

Jawale, Chetan V. ^{[1
]}

Wu, Dongwen ^{[1
]}

Rittenhouse, Natalie ^{[2
]}

Menk, Ashley ^{[3
]}

Kupul, Saran ^{[1
]}

Du, Fang ^{[1
]}

Raphael, Itay ^{[1
]}

Bhattacharjee, Amrita ^{[2
]}

Siebenlist, Ulrich ^{[4
]}

Hand, Timothy W. ^{[2
]}

Delgoffe, Greg M. ^{[3
]}

Poholek, Amanda C. ^{[2
]}

Gaffen, Sarah L. ^{[1
]}

Biswas, Partha S. ^{[1
]}

McGeachy, Mandy J. ^{[1
]}

机构：

[1] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15261 USA

[2] Univ Pittsburgh, Dept Pediat, Pittsburgh, PA 15260 USA

[3] Univ Pittsburgh, Tumor Microenvironm Ctr, UPMC Hillman Canc Ctr, Pittsburgh, PA USA

[4] NIAID, Immune Activat Sect, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA

来源：

NATURE IMMUNOLOGY | 2019年 / 20卷 / 05期

基金：

美国安德鲁·梅隆基金会;

关键词：

T-HELPER-CELLS; TH17; CELLS; SIGNALING PATHWAY; GENE; INTERLEUKIN-17; RECEPTOR; INFLAMMATION; POPULATIONS; HOMEOSTASIS; EXPRESSION;

D O I：

10.1038/s41590-019-0367-4

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

Lymph-node (LN) stromal cell populations expand during the inflammation that accompanies T cell activation. Interleukin-17 (IL-17)-producing helper T cells (T(H)17 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 T(H)17 cells, but failed FRC proliferation impaired germinal center formation and antigen-specific antibody production. Induction of the transcriptional co-activator I kappa B zeta 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 T(H)17 cells is an important driver of the activation of inflamed LN stromal cells, through metabolic reprogramming required to support proliferation and survival.

引用

页码：534 / +

页数：14

共 56 条

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