Medical College of Wisconsin
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Conventional CD4+ T cells regulate IL-22-producing intestinal innate lymphoid cells. Mucosal Immunol 2014 Sep;7(5):1045-57

Date

01/23/2014

Pubmed ID

24448096

Pubmed Central ID

PMC4107180

DOI

10.1038/mi.2013.121

Scopus ID

2-s2.0-84900485129 (requires institutional sign-in at Scopus site)   71 Citations

Abstract

The innate and adaptive immune systems in the intestine cooperate to maintain the integrity of the intestinal barrier and to regulate the composition of the resident microbiota. However, little is known about the crosstalk between the innate and adaptive immune systems that contribute to this homeostasis. We find that CD4+ T cells regulate the number and function of barrier-protective innate lymphoid cells (ILCs), as well as production of antimicrobial peptides (AMPs), Reg3γ and Reg3β. RAG1-/- mice lacking T and B cells had elevated ILC numbers, interleukin-22 (IL-22) production, and AMP expression, which were corrected by replacement of CD4+ T cells. Major histocompatibility class II-/- (MHCII-/-) mice lacking CD4+ T cells also had increased ILCs, IL-22, and AMPs, suggesting that negative regulation by CD4+ T cells occurs at steady state. We utilized transfers and genetically modified mice to show that reduction of IL-22 is mediated by conventional CD4+ T cells and is T-cell receptor dependent. The IL-22-AMP axis responds to commensal bacteria; however, neither the bacterial repertoire nor the gross localization of commensal bacteria differed between MHCII+/- and MHCII-/- littermates. These data define a novel ability of CD4+ T cells to regulate intestinal IL-22-producing ILCs and AMPs.

Author List

Korn LL, Thomas HL, Hubbeling HG, Spencer SP, Sinha R, Simkins HM, Salzman NH, Bushman FD, Laufer TM

Author

Nita H. Salzman MD, PhD Center Director, Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adaptive Immunity
Animals
Antimicrobial Cationic Peptides
CD4-Positive T-Lymphocytes
Genes, RAG-1
Immunity, Innate
Interleukins
Intestines
Lymphocytes
Mice
Mice, Knockout