Fig. 3.

Major functions of lung-resident Tregs in the regulation of epithelial SCs. In the lungs, the alveolar epithelium is lined by AEC1s, which differentiate from AEC2s. The maintenance of AEC2s is partially regulated by Notch signalling activities. As such, it presents a possibility that Jagged1-expressing Tregs regulate AEC2 differentiation. A Treg-secreted molecule, amphiregulin, has been associated with restoration of barrier function in the lungs. However, whether Tregs are the primary source of amphiregulins in the lungs, and whether the functional recovery of the lungs were achieved as a result of epithelial stem cell proliferation, or deposition of extracellular matrix proteins, is incompletely addressed. Studies thus far suggest a dual role for amphiregulin. Amphiregulin has been shown to promote the differentiation of fibroblasts into myofibroblasts, which are specialised in remodelling the extracellular matrix. Additionally, recombinant amphiregulin protects AEC2s from apoptosis. Brown arrows indicate findings from in vitro studies.