TGF-β can leave you breathless

Transforming growth factor-beta (TGF-β), a ubiquitous and multifunctional cytokine, is central to the evolution and modulation of host defense. Early on, TGF-β was recognized for its chemotactic and pro-inflammatory properties, but then identification of its powerful suppressive activities focused attention on dissecting its mechanisms of immune inhibition. Just as quickly as TGF-β-mediated regulation of a population of CD4+CD25+Foxp3+ regulatory T cells became the rage, a surprising finding that TGF-β was the impetus behind a subset of pro-inflammatory T helper (Th)17 cells brought back a re-emphasis on its broader ability to dictate inflammatory events. Emerging evidence indicates that much remains to be discovered regarding the complex and intertwined roles of TGF-β in inflammation, T cell lineage commitment, antibody generation, immune suppression, and tolerance. While it may appear that TGF-β has multiple, ill-defined, contradictory and overlapping modes of activity that are impossible to unravel, the current excitement for dissecting how TGF-β controls immunity defines a challenge worthy of pursuit. The lung is particularly vulnerable to the influences of TGF-β, which is produced by its immune and non-immune cell populations. In its absence, lung pathology becomes lethal, whereas TGF-β overproduction also has untoward consequences, potentially leaving one breathless, and underscoring the paradoxical, but essential contribution of TGF-β to tissue and immune homeostasis.