Regulatory T (Treg) cells, a CD4+ T lymphocyte subset that expresses the lineage-specifying transcription factor Foxp3, play a critical role in suppressing overexuberant immune system activation and maintaining immune homeostasis (1, 2). Treg cells exert their immune regulatory activities via myriad mechanisms, including ligand-receptor interactions, metabolic disruption, cytolysis, and elaboration of soluble mediators that suppress the activation and proliferation of multiple immune cell types such as other T lymphocytes and antigen-presenting cells. These suppressor functions require continuous signaling through the Treg T cell receptor (TCR)(3). Beyond limiting collateral damage associated with unrestrained immune-mediated inflammation (4, 5), Treg cells also exert recently understood actions that directly repair injured tissues. These pro-repair functions appear to manifest independently of their suppressor functions. For example, Treg cells accumulate after muscle injury and elaborate factors such as amphiregulin, an epidermal growth factor receptor ligand that acts on muscle satellite cells to promote repair (6). Treg cell–derived amphiregulin also protects murine lung tissue against influenza A infection in a TCR-independent manner (7). Alveolar epithelial cell proliferation represents a hallmark feature of active repair after lung injury (8). Mock and colleagues established that Treg cells serve as a critical determinant of alveolar type II epithelial (AT2) cell proliferation after an inflammatory lung injury (intratracheal administration of LPS) as well as in a noninflammatory model of compensatory lung growth/regenerative alveologenesis (unilateral pneumonectomy)(9). In that study they also determined that contact-independent (soluble) factors account, in part, for the proliferative effect of Treg cells on AT2 cells. However, these factors’ identities remained unknown.

Keratinocyte growth factor (kgf, also known as fibroblast growth factor 7 [Fgf7]) signals through the Fgfr2b receptor and leads to cell proliferation (10). In this issue of the Journal, Dial and colleagues (pp. 162–173) report the results of elegant experiments demonstrating that Treg cell–derived kgf promotes AT2 cell proliferation (11). The authors employed powerful multiparameter flow cytometry to define lung epithelial cell populations, including ciliated, club, AT1, and AT2 cells. They did not evaluate lineagenegative epithelial stem/progenitor cells, which the lung deploys to regenerate the epithelium after severe injury (12). Nevertheless, their data show that global kgf deficiency causes a decrease in overall epithelial as well as AT2 cell proliferation during resolution of intratracheal LPS-induced acute lung injury. kgf was not necessary for recovery of weight loss after LPS; thus, although they were not explored in this article, other mediators appear to ensure