TY - JOUR
T1 - Lymphotoxin controls the IL-22 protection pathway in gut innate lymphoid cells during mucosal pathogen challenge
AU - Tumanov, Alexei V.
AU - Koroleva, Ekaterina P.
AU - Guo, Xiaohuan
AU - Wang, Yugang
AU - Kruglov, Andrei
AU - Nedospasov, Sergei
AU - Fu, Yang Xin
N1 - Funding Information:
This research was, in part, supported by US National Institutes of Health grants AI062026, CA115540, and DK58891 to Y.-X.F; by a Career Development Award from the Crohn's and Colitis Foundation (CCFA #2672) to A.V.T.; by SFB633 from Deutsche Forschungs gemeinschaft; and by the MCB Program of the Russian Academy of Sciences. We are grateful to W. Ouyang (Genentech, CA) for providing IL-22-expressing plasmid and anti-IL-22 antibody; D. Littman and I. Ivanov (New York University, NY) for RORγt-Cre mice and hamster anti-RORγt antibody; C. Ware (La Jolla Institute for Allergy and Immunology, CA) for 3C8 LTβR antibody; and A. Chervonsky (University of Chicago, IL) for CD11c-Cre mice. We thank M. Miller for critical reading of the manuscript.
PY - 2011/7/21
Y1 - 2011/7/21
N2 - Innate lymphoid cells (ILCs) have emerged as important players, regulating the balance between protective immunity and immunopathology at mucosal surfaces. However, mechanisms that regulate ILCs' effector functions during mucosal pathogenic challenge are poorly defined. Using mice infected with the natural mouse enteric pathogen Citrobacter rodentium, we demonstrate that lymphotoxin (LT) is essential for IL-22 production by intestinal ILCs. Blocking of LTβR signaling dramatically reduced intestinal IL-22 production after C. rodentium infection. Conversely, stimulating LTβR signaling induced an IL-22 protection pathway in LT-deficient mice. Furthermore, exogenous IL-22 expression rescued LTβR-deficient mice. IL-22-producing ILCs were predominantly located in lymphoid follicles in the colon and interacted closely with dendritic cells (DCs). We find that an LT-driven positive feedback loop controls IL-22 production by RORγt + ILCs via LTβR signaling in DCs. Taken together, our data show that LTβR signaling in gut lymphoid follicles regulates IL-22 production by ILCs in response to mucosal pathogen challenge.
AB - Innate lymphoid cells (ILCs) have emerged as important players, regulating the balance between protective immunity and immunopathology at mucosal surfaces. However, mechanisms that regulate ILCs' effector functions during mucosal pathogenic challenge are poorly defined. Using mice infected with the natural mouse enteric pathogen Citrobacter rodentium, we demonstrate that lymphotoxin (LT) is essential for IL-22 production by intestinal ILCs. Blocking of LTβR signaling dramatically reduced intestinal IL-22 production after C. rodentium infection. Conversely, stimulating LTβR signaling induced an IL-22 protection pathway in LT-deficient mice. Furthermore, exogenous IL-22 expression rescued LTβR-deficient mice. IL-22-producing ILCs were predominantly located in lymphoid follicles in the colon and interacted closely with dendritic cells (DCs). We find that an LT-driven positive feedback loop controls IL-22 production by RORγt + ILCs via LTβR signaling in DCs. Taken together, our data show that LTβR signaling in gut lymphoid follicles regulates IL-22 production by ILCs in response to mucosal pathogen challenge.
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U2 - 10.1016/j.chom.2011.06.002
DO - 10.1016/j.chom.2011.06.002
M3 - Article
C2 - 21767811
AN - SCOPUS:79960500206
SN - 1931-3128
VL - 10
SP - 44
EP - 53
JO - Cell Host and Microbe
JF - Cell Host and Microbe
IS - 1
ER -