T_reg cell division of labor

The relative contributions of inducible regulatory T cells (iT_reg cells) and thymus-derived regulatory T cells (nT_reg cells) to various aspects of immune homeostasis remain unclear. In Nature, Rudensky and colleagues show that deficiency in iT_reg cells does not lead to systemic or tissue-specific autoimmune pathology or enhanced proinflammatory responses of helper T cells of the T_H1 or T_H17 subset but leads to spontaneous T helper type 2 (T_H2) pathologies at mucosal sites. The authors use mice deficient in the transforming growth factor-β (TGF-β) enhancer CNS1, which cannot induce expression of the transcription factor Foxp3 dependent on TGF-β, and as a consequence have no iT_reg cells, although the number of nT_reg cells is normal. CNS1-deficient mice show dysregulated T_H2 responses that lead to spontaneous inflammation of the airway and gastrointestinal tract. Loss of T_H2 homeostasis leads to perturbations in the composition of the microbial community in the gut. These results suggest that nT_reg and iT_reg cells not only have distinct mechanistic requirements for differentiation but also specific functions in immune homeostasis.

Nature (8 February 2012) doi:10.1038/nature10772