Foxp3+CD4+ regulatory T cells (Tregs) control most types of immune responses. Largely due to the ease with which we can access them, our view of Treg generation, phenotype and function is heavily colored by observations on cells found in lymphoid organs, in particular the spleen and lymph nodes. Our lab has been studying Tregs that infiltrate diverse tissues, eg the pancreas, adipose tissue, skeletal muscle and the large intestine. These “tissue-Treg” populations have distinct properties, adapted to their particular microenvironment and job. Interestingly, tissue-Tregs not only impact immunocyte responses taking place in the vicinity, but can also influence non-immune processes. This presentation will focus on the diversification of tissue-Tregs and their sustenance by IL-33-producing mesenchymal stromal cells.