Universität zu Köln

DiToro, Daniel, Harbour, Stacey N., Bando, Jennifer K., Benavides, Gloria, Witte, Steven, Laufer, Vincent A., Moseley, Carson, Singer, Jeffery R., Frey, Blake, Turner, Henrietta, Bruning, Jens, Darley-Usmar, Victor, Gao, Min, Conover, Cheryl, Hatton, Robin D., Frank, Stuart, Colonna, Marco and Weaver, Casey T. (2020). Insulin-Like Growth Factors Are Key Regulators of T Helper 17 Regulatory T Cell Balance in Autoimmunity. Immunity, 52 (4). S. 650 - 678. CAMBRIDGE: CELL PRESS. ISSN 1097-4180

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Abstract

Appropriate balance of T helper 17 (Th17) and regulatory T (Treg) cells maintains immune tolerance and host defense. Disruption of Th17-Treg cell balance is implicated in a number of immune-mediated diseases, many of which display dysregulation of the insulin-like growth factor (IGF) system. Here, we show that, among effector T cell subsets, Th17 and Treg cells selectively expressed multiple components of the IGF system. Signaling through IGF receptor (IGF1R) activated the protein kinase B-mammalian target of rapamycin (AKT-mTOR) pathway, increased aerobic glycolysis, favored Th17 cell differentiation over that of Treg cells, and promoted a heightened pro-inflammatory gene expression signature. Group 3 innate lymphoid cells (ILC3s), but not ILC1s or ILC2s, were similarly responsive to IGF signaling. Mice with deficiency of IGF1R targeted to T cells failed to fully develop disease in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis. Thus, the IGF system represents a previously unappreciated pathway by which type 3 immunity is modulated and immune-mediated pathogenesis controlled.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code DiToro, Daniel UNSPECIFIED UNSPECIFIED UNSPECIFIED Harbour, Stacey N. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bando, Jennifer K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Benavides, Gloria UNSPECIFIED UNSPECIFIED UNSPECIFIED Witte, Steven UNSPECIFIED UNSPECIFIED UNSPECIFIED Laufer, Vincent A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Moseley, Carson UNSPECIFIED UNSPECIFIED UNSPECIFIED Singer, Jeffery R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Frey, Blake UNSPECIFIED UNSPECIFIED UNSPECIFIED Turner, Henrietta UNSPECIFIED UNSPECIFIED UNSPECIFIED Bruning, Jens UNSPECIFIED UNSPECIFIED UNSPECIFIED Darley-Usmar, Victor UNSPECIFIED UNSPECIFIED UNSPECIFIED Gao, Min UNSPECIFIED UNSPECIFIED UNSPECIFIED Conover, Cheryl UNSPECIFIED UNSPECIFIED UNSPECIFIED Hatton, Robin D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Frank, Stuart UNSPECIFIED UNSPECIFIED UNSPECIFIED Colonna, Marco UNSPECIFIED UNSPECIFIED UNSPECIFIED Weaver, Casey T. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-337189
DOI:	10.1016/j.immuni.2020.03.013
Journal or Publication Title:	Immunity
Volume:	52
Number:	4
Page Range:	S. 650 - 678
Date:	2020
Publisher:	CELL PRESS
Place of Publication:	CAMBRIDGE
ISSN:	1097-4180
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language FACTOR-I RECEPTOR; FACTOR BINDING-PROTEINS; CYTOKINE GM-CSF; TH17 CELLS; GRAVES-DISEASE; BONE-MARROW; MULTIPLE-SCLEROSIS; MAMMALIAN TARGET; TGF-BETA; IGF-I Multiple languages Immunology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/33718