Lymphotoxin controls the IL-22 protection pathway in gut innate lymphoid cells during mucosal pathogen challenge
- PMID: 21767811
- PMCID: PMC3375029
- DOI: 10.1016/j.chom.2011.06.002
Lymphotoxin controls the IL-22 protection pathway in gut innate lymphoid cells during mucosal pathogen challenge
Abstract
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.
Copyright © 2011 Elsevier Inc. All rights reserved.
Conflict of interest statement
Authors declare no conflicts of interest.
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Comment in
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Another armament in gut immunity: lymphotoxin-mediated crosstalk between innate lymphoid and dendritic cells.Cell Host Microbe. 2011 Jul 21;10(1):3-4. doi: 10.1016/j.chom.2011.07.002. Cell Host Microbe. 2011. PMID: 21767806
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