T-cell differentiation leads to cells that can be distinguished by functional assays and their production of characteristic cytokines. This cellular differentiation is commonly viewed as a kind of lineage commitment associated with the expression of master regulators within this process, i.e. the transcription factors T-bet, Gata-3, RorγT, Bcl6, and FoxP3 that drive differentiation of Th1, Th2, Th17, follicular T helper (Tfh), and regulatory Treg cells, respectively. However, Inhibitor Library supplier there is growing evidence for plasticity

in this process, and in the context of Th cell function in chronic infections such as H. pylori, one should keep in mind that subtype populations may not be as committed as generally believed [38]. The generation and maintenance of a T-cell response depends on DC, and it has been a longstanding challenge to decipher whether DCs are present in noninflamed gastric mucosa. Studies in mice had shown that H. pylori-specific responses might be induced more

distally in the gastrointestinal system, in Peyer’s patches, by passing H. pylori, implying that this was a functional consequence of the gastric mucosa lacking DC [39,40]. Several groups have now re-addressed this issue. Bimczok et al. [41] showed that cells with typical DC markers such as MHC selleck chemicals llc II, CD11c, DC-SIGN, and CD206 can be isolated from biopsies taken from both normal and H. pylori-infected patients. The frequency of these cells increased around fivefold in biopsies from infected patients in which DCs also exhibited an activated phenotype and molecules which act as co-stimulatory ligands to T cells, such as CD86, were upregulated. In vitro, these gastric DCs phagocytose and process H. pylori. DCs secreted IL-6, -8, and

-10 as well as triggering expansion of Th1 cells. Presence of DCs in normal human gastric mucosa and their increase in H. pylori colonized mucosa were confirmed by Necchi et al. [42]. It is interesting in this context that Khamri et al. also detected monocyte-derived DCs in inflamed mucosa, and using DCs derived by IL-4 and GM-CSF from blood monocytes, they found that these cells express IL-23 and IL-12, but the former was produced earlier [43]. IL-23 is a positive regulator of Th17 cells, and Kamzi et al. could visualize IL-23 上海皓元 expressing DCs as well as Th17 cell in inflamed gastric mucosa. They also showed that in vitro stimulated CD4+ T cells produce more IL-17 in response to H. pylori exposed DCs, a process mediated by IL-23 and IL-1. Kao et al. reported essentially similar findings when analyzing mice [44]. They showed that bone marrow-derived DCs (which are more accessible) preferentially induced Treg and Th17 cells. Differentiation of these CD4+ subsets requires TGF-β, but Th17 cells also need IL-6 and are further promoted by IL-23 and IL-1. The bias toward Treg cells in the murine system was probably because H.