Regulatory T cells and type 2 innate lymphoid cell‐dependent asthma

Abstract Group 2 innate lymphoid cells ( ILC 2s) are a recently identified group of cells with the potent capability to produce Th2‐type cytokines such as interleukin ( IL )‐5 and IL ‐13. Several studies suggest that ILC 2s play an important role in the development of allergic diseases and asthma. Activation of pulmonary ILC 2s in murine models lacking T and B cells induces eosinophilia and airway hyper‐reactivity ( AHR ), which are cardinal features of asthma. More importantly, numerous recent studies have highlighted the role of ILC 2s in asthma persistence and exacerbation among human subjects, and thus, regulation of pulmonary ILC 2s is a major area of investigation aimed at curbing allergic lung inflammation and exacerbation. Emerging evidence reveals that a group of regulatory T cells, induced Tregs ( iT regs), effectively suppress the production of ILC 2‐driven, pro‐inflammatory cytokines IL ‐5 and IL ‐13. The inhibitory effects of iT regs are blocked by preventing direct cellular contact or by inhibiting the ICOS ‐ ICOS ‐ligand ( ICOSL ) pathway, suggesting that both direct contact and ICOS ‐ ICOSL interaction are important in the regulation of ILC 2 function. Also, cytokines such as IL ‐10 and TGF ‐β1 significantly reduce cytokine secretion by ILC 2s. Altogether, these new findings uncover iT regs as potent regulators of ILC 2 activation and implicate their utility as a therapeutic approach for the treatment of ILC 2‐mediated allergic asthma and respiratory disease.