Food antigens, not microbiota, regulate Foxp3+ regulatory T cells in small intestine

Foxp3⁺ regulatory T cells, shortly Tregs, are an unique subset of CD4 T cells that regulate magnitude and possibly class of immune response. 

In general, Tregs are divided into two subsets referred as thymus-derived Tregs (tTregs) and peripheral tissue-induced Tregs (pTregs). Historically speaking, this division of Tregs is arbitrary [it is assumed that thymus alone could not generate Tregs specific for peripheral antigens, such as tissue-specific antigens or food derived antigens] but till today we have no definite proof whether there is indeed such a thing as a peripheral Tregs.

In this regard new Science paper is of interest. In this "observation" type paper, the authors reported that food antigens, not microbiota, played important role in regulation of small intestinal Tregs, while the reverse was true for large intestinal Tregs.

I would like to point out that in this study the authors have used Neuropilin-1 (Nrp-1) to differentiate between tTregs and pTregs. However, more recent studies questioned the validity of this marker. So, for me, the results in this paper are simply "observations", not necessary "mechanisms".

The main contribution of this study is the use of antigen-free diet [chemically defined food devoid of macro-molecules] to analyse Tregs physiology in mice. It showed that mice on antigen-free diet had reduced number of Tregs in small intestinal tissue (but not in spleen or large intestine).

Next, the authors reported that small intestine of mice fed with antigen-free diet lacked Tregs expressing low level of Neuropilin-1 (that according to the authors represent peripheral Tregs). At least, these results indicate that food derived antigens regulate the fate of Neuropilin-1^low Tregs in small intestine.

Finally, by transferring ovalbumin-specific OT-II CD4 T cells in mice fed with antigen-free diet, the authors showed that lack of host Neuropilin-1^low Tregs in small intestine could lead to excessive proliferation of donor antigen-specific T cells in these mice (that could lead to exaggerated, allergic-type immune response).

In summary, this study showed that solid food derived antigens are important in regulating physiology of small intestinal Tregs. This knowledge could help to understand how food allergies develop.

David Usharauli