TY - JOUR
T1 - InterleuKin-33 And Interferon-Γ Counter-Regulate Group 2 Innate Lymphoid Cell Activation During Immune Perturbation
AU - Molofsky, Ari B.
AU - Van Gool, Frédéric
AU - Liang, Hong Erh
AU - Van Dyken, Steven J.
AU - Nussbaum, Jesse C.
AU - Lee, Jinwoo
AU - Bluestone, Jeffrey A.
AU - Locksley, Richard M.
N1 - Funding Information:
We thank Drs. S. Akira, J.-P. Girard, A. DeFranco, and A. Rudensky for mice; Drs. A. DeFranco, A. Abbas, and C. Lowell for comments on the manuscript; Z.-E. Wang for technical assistance; and G. Rizzuto and J.D. Sauer for assistance with Listeria infections. This work was supported by AI026918, AI030663, AI078869, HL107202, and K08DK101604 (A.B.M.) from the NIH, the UCSF Diabetes Family Fund (A.B.M.), the UCSF REAC Pilot Grant (A.B.M.), the Sandler Asthma Basic Research Center at UCSF, and the Howard Hughes Medical Institute.
Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2015/7/21
Y1 - 2015/7/21
N2 - Group 2 innate lymphoid cells (ILC2s) and regulatory T (Treg) cells are systemically induced by helminth infection but also sustain metabolic homeostasis in adipose tissue and contribute to tissue repair during injury. Here we show that interleukin-33 (IL-33) mediates activation of ILC2s and Treg cells in resting adipose tissue, but also after helminth infection or treatment with IL-2. Unexpectedly, ILC2-intrinsic IL-33 activation was required for Treg cell accumulation invivo and was independent of ILC2 type 2 cytokines but partially dependent on direct co-stimulatory interactions via ICOSL-ICOS. IFN-γ inhibited ILC2 activation and Treg cell accumulation by IL-33 in infected tissue, as well as adipose tissue, where repression increased with aging and high-fat diet-induced obesity. IL-33 and ILC2s are central mediators of type 2 immune responses that promote tissue and metabolic homeostasis, and IFN-γ suppresses this pathway, likely to promote inflammatory responses and divert metabolic resources necessary to protect the host.
AB - Group 2 innate lymphoid cells (ILC2s) and regulatory T (Treg) cells are systemically induced by helminth infection but also sustain metabolic homeostasis in adipose tissue and contribute to tissue repair during injury. Here we show that interleukin-33 (IL-33) mediates activation of ILC2s and Treg cells in resting adipose tissue, but also after helminth infection or treatment with IL-2. Unexpectedly, ILC2-intrinsic IL-33 activation was required for Treg cell accumulation invivo and was independent of ILC2 type 2 cytokines but partially dependent on direct co-stimulatory interactions via ICOSL-ICOS. IFN-γ inhibited ILC2 activation and Treg cell accumulation by IL-33 in infected tissue, as well as adipose tissue, where repression increased with aging and high-fat diet-induced obesity. IL-33 and ILC2s are central mediators of type 2 immune responses that promote tissue and metabolic homeostasis, and IFN-γ suppresses this pathway, likely to promote inflammatory responses and divert metabolic resources necessary to protect the host.
UR - http://www.scopus.com/inward/record.url?scp=84937618997&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2015.05.019
DO - 10.1016/j.immuni.2015.05.019
M3 - Article
C2 - 26092469
AN - SCOPUS:84937618997
SN - 1074-7613
VL - 43
SP - 161
EP - 174
JO - Immunity
JF - Immunity
IS - 1
ER -