Tuesday, June 7, 2016

Runx3-dependent intraepithelial lymphocytes (CD4IELs) control gut tolerance to dietary antigens

Few days ago journal Science published another immunological study. This hard to read research paper showed that special subset of Foxp3–CD8αα+CD4+ intraepithelial lymphocytes (CD4IELs) found within intestinal epithelium play distinct and dominant role in preventing gut inflammation to dietary antigens.

It appears that induction or maintenance of Foxp3–CD8αα+CD4+ intraepithelial lymphocytes (CD4IELs) depends on antigens derived from either from gut flora [microbiome] or food.

The main finding of this paper was observation that antigen-specific T cell monoclonal mouse strain deficient for Foxp3 expression [but not Foxp3 wt] depleted of CD4IELs using anti-CD8α antibodies during antigen feeding showed severe intestinal inflammation and diarrhea. It suggests Foxp3–CD8αα+CD4+ intraepithelial lymphocytes (CD4IELs) play distinct and separate [that from Foxp3wt T cells] role in protecting intestinal tissue against antigenic inflammation.

Why is this paper relevant? For one, it indicates that tolerance to food antigens in physiological situations, for example during feeding, could be mediated by Foxp3–CD8αα+CD4+ intraepithelial lymphocytes (CD4IELs), and not by Foxp3+ CD4+ T cells, as scientists ordinarily assume. However, for now, we know relatively little about tissue-resident innate-like or adaptive-like cells, such as these Foxp3–CD8αα+CD4+ intraepithelial lymphocytes (CD4IELs).

David Usharauli

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