Treg regulation of the epithelial stem cell lineage

Tissue repair and maintenance in adult organisms is dependent on the interactions between stem cells (SCs) and constituent cells of their microenvironment, or niche. Accumulating evidence suggests that immune cells, specifically Foxp3⁺ CD4⁺ Regulatory T cells (Tregs), play an important role as a regulator of the SC niche. Undisputedly, Tregs are the major immunosuppressive lineage of the CD4⁺ T cell compartment, and reside within numerous secondary lymphoid organs, where they exert their functions. These cells are also specialised in facilitating protective functions specific to their tissue of residence. In this review, we discuss the emerging concepts supporting the SC-regulatory functions of tissue-resident Tregs, during both the steady-state and SC-mediated regeneration. We highlight the skin, intestines, and lung as model organs which are subject to recurrent microinjury,exposure to microbiota, and constantly replenished by resident stem cell populations. An in-depth understanding of the biology of the Treg-SC axis will inform ongoing immunotherapeutic endeavours to target specific subpopulations of tissue-resident Tregs.