TY - JOUR
T1 - Innate Lymphoid Cells Control Early Colonization Resistance against Intestinal Pathogens through ID2-Dependent Regulation of the Microbiota
AU - Guo, Xiaohuan
AU - Liang, Yong
AU - Zhang, Yuan
AU - Lasorella, Anna
AU - Kee, Barbara L.
AU - Fu, Yang Xin
N1 - Funding Information:
We are grateful to D. Littman (New York University) for Rorc cre mice, L. Zhou (Northwestern University) for the AhR plasmid, C.R. Nagler (The University of Chicago) for germ-free mice, A.T. Stefka (The University of Chicago) for the analysis of pyrosequencing with bacterial 16S rRNA genes, and W. Ouyang (Genentech) for anti-IL-22 antibody. The work was supported by NIH grants AI106352 (to B.L.K.) and DK080736, DK095962, and DK100427 (to Y.X.F.).
Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2015/4/21
Y1 - 2015/4/21
N2 - Microbiota-mediated effects on the host immune response facilitate colonization resistance against pathogens. However, it is unclear whether and how the host immune response can regulate the microbiota to mediate colonization resistance. ID2, an essential transcriptional regulator for the development of innate lymphoid cell (ILC) progenitors, remains highly expressed in differentiated ILCs with unknown function. Using conditionally deficient mice in which ID2 is deleted from differentiated ILC3s, we observed that these mutant mice exhibited greatly impaired gut colonization resistance against Citrobacter rodentium. Utilizing gnotobiotic hosts, we showed that the ID2-dependent early colonization resistance was mediated by interleukin-22 (IL-22) regulation of the microbiota. In addition to regulating development, ID2 maintained homeostasis of ILC3s and controlled IL-22 production through an aryl hydrocarbon receptor (AhR) and IL-23 receptor pathway. Thus, ILC3s can mediate immune surveillance, which constantly maintains a proper microbiota, to facilitate early colonization resistance through an ID2-dependent regulation of IL-22.
AB - Microbiota-mediated effects on the host immune response facilitate colonization resistance against pathogens. However, it is unclear whether and how the host immune response can regulate the microbiota to mediate colonization resistance. ID2, an essential transcriptional regulator for the development of innate lymphoid cell (ILC) progenitors, remains highly expressed in differentiated ILCs with unknown function. Using conditionally deficient mice in which ID2 is deleted from differentiated ILC3s, we observed that these mutant mice exhibited greatly impaired gut colonization resistance against Citrobacter rodentium. Utilizing gnotobiotic hosts, we showed that the ID2-dependent early colonization resistance was mediated by interleukin-22 (IL-22) regulation of the microbiota. In addition to regulating development, ID2 maintained homeostasis of ILC3s and controlled IL-22 production through an aryl hydrocarbon receptor (AhR) and IL-23 receptor pathway. Thus, ILC3s can mediate immune surveillance, which constantly maintains a proper microbiota, to facilitate early colonization resistance through an ID2-dependent regulation of IL-22.
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U2 - 10.1016/j.immuni.2015.03.012
DO - 10.1016/j.immuni.2015.03.012
M3 - Article
C2 - 25902484
AN - SCOPUS:84928194546
SN - 1074-7613
VL - 42
SP - 731
EP - 743
JO - Immunity
JF - Immunity
IS - 4
ER -