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Th17 cells; friend or foe in intestinal homeostasis?
Hegazy AN, West NR, Stubbington MJT, et al. Circulating and tissue-resident CD4+ T cells with reactivity to intestinal microbiota are abundant in healthy individuals and function is altered during inflammation. Gastroenterology 2017 Aug. pii: S0016-5085(17)35979-6. doi: 10.1053/j.gastro.2017.07.047. (Epub ahead of print).
Intestinal immune responses are tightly regulated to provide the necessary protection against pathogenic organisms while controlling responses to commensal species. Characterising T cell responses to bacteria is an important aspect of the puzzle. In humans, circulating memory T cells recognise peptides derived from gut bacteria and can cross-react to pathogens. While the process may be beneficial during homeostasis, this potentially contributes to inflammatory conditions such as IBD when regulatory aspects are dysfunctional. Currently, there is a lack of knowledge regarding the type, frequency and functional phenotype of T cells that react to intestinal microbes in the gut and how these immune cells change during chronic intestinal inflammation. This study by Hegazy and colleagues used a combination of experimental approaches to address these questions. The data demonstrate that circulating enteric bacteria-reactive CD4+ T cells co-express chemokine receptors including CCR4, CCR6 and CCR7, with a smaller fraction also expressing gut-related homing receptors α4β7 and CCR9 promoting access to secondary lymphoid organs. The microbiota-reactive T cells displayed Th17 and Th1 characteristics and in some cases produced interleukin (IL)-10. A clear Th17 bias was seen in gut-resident cells in IBD although these observations were also evident in healthy individuals. The authors suggest that the continuous luminal sampling of the intestinal microbiota and response to epithelial breaches, such as during an infection, provides a plethora of memory T cells with potential reactivity towards newly encountered pathogens. Therefore, contrary to previous assumptions, these T cells may actually be promoting intestinal homeostasis rather than inflammation.
Inflammatory responses in NAFLD
Hart KM, Fabre T, Sciurba JC, et al. Type two immunity …
Contributors Georgina Hold, Richard Parker, Mairi McLean, Sebastian Zeki, Michael Burkitt, Ashis Mukhopadhya.
Competing interests None declared.
Provenance and peer review Not commissioned; internally peer reviewed.
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