Th22 Cells Are an Important Source of IL-22 for Host Protection against Enteropathogenic Bacteria

Abstract

SUMMARY Interleukin-22 (IL-22) is central to host protection against bacterial infections at barrier sites. Both innate lymphoid cells (ILCs) and T cells produce IL-22. However, the specific contributions of CD4+ T cells and their developmental origins are unclear. We found that the enteric pathogen Citrobacter rodentium induced sequential waves of IL-22 producing ILCs and CD4+ T cells that were each critical to host defense during a primary infection. Whereas IL-22 production by ILCs was strictly IL-23–dependent, development of IL-22 producing CD4+ T cells occurred via an IL-6–dependent mechanism that was augmented by, but not dependent on, IL-23, and was dependent on both transcription factors T-bet and AhR. Transfer of CD4+ T cells differentiated with IL-6 in the absence of TGF-β (“Th22” cells) conferred protection of infected IL-22-deficient mice whereas transferred Th17 cells did not. These findings establish Th22 cells as an important component of mucosal anti-microbial host defense.

Mechanisms of NDV-3 vaccine efficacy in MRSA skin versus invasive infection

“…Our results are congruent with recent reports supporting a key function of T cells and the Th17 pathway (including IL-17 family, IL-22, and IL-23 cytokines) in defense against infections at skin and mucocutaneous barriers (59)(60)(61)(62)(63)(64)(65)(66). Corticosteroid inhibition of IL-22 production has been associated with impaired barrier protection and increased bacterial invasion (67).…”

Chronic mTOR inhibition in mice with rapamycin alters T, B, myeloid, and innate lymphoid cells and gut flora and prolongs life of immune‐deficient mice

“…We challenged 8‐month‐old mice on eRapa for 6 months with flagel‐lin, which augments IL‐23‐driven IL‐22 from intestinal group 3 ILC (Basu  et al ., 2012). Mice on eRapa experienced eightfold increased flagellin‐driven serum IL‐22 versus Eudragit (Fig.…”

“…6D). As IL‐22‐producing group 3 ILCs protect from intestinal bacterial infection, we challenged RAG2 −/− mice on eRapa or Eudragit for 1 month with the flagellated bacterium C. rodentium as described (Basu et al ., 2012). eRapa did not protect from chronic infection as determined by survival, weight change, and colon length (Fig.…”

Molecular cloning, expression analysis and functional characterization of interleukin-22 in So-iny mullet, Liza haematocheila

“…In mammals, IL-22 plays an important role in the development of chronic inflammatory diseases and in preventing tissue damage, acting as a T H -17 cytokine (Zheng et al, 2007;Ma et al, 2008). Recently, it has been found that IL-22 can enhance mucosal barrier function (Basu et al, 2012;Leung and Loke, 2012), and activate antimicrobial defense in host by inducing the expression of antimicrobial peptides (AMPs), such as ␤-defensins 2 and 3 (Liang et al, 2006). IL-22 has been identified in many lower vertebrate species, such as zebrafish (Danio rerio) (Igawa et al, 2006), rainbow trout (Oncorhynchus mykiss) (Monte et al, 2011), and the amphibian Xenopus tropicalis (Qi and Nie, 2008).…”