The role of innate T cells in inflammatory disorders in asthma and chronic rhinosinusitis.

Abstract

Chronic rhinosinusitis (CRS) and asthma are often comorbid and represent heterogeneous inflammatory disorders in the upper and lower airways, respectively. Type 2 inflammation driven by eosinophils and CD4 T cells has been recognized as central mediators in CRS with nasal polyp (CRSwNP) and asthma pathogenesis. However, recent evidence has highlighted the critical involvement of innate T cells, such as invariant natural killer T (iNKT), mucosal-associated invariant T (MAIT), and γδ T cells in airway inflammatory disorders. Innate T cells were enriched in sinonasal tissues and contributed to mucosal inflammation through cytokine production, exhibiting functional polarization influenced by local inflammatory cues. In particular, MAIT17 and Vγ1+ γδ T cells have been associated with tissue eosinophilia and disease severity in eosinophilic CRSwNP (E-NP) patients, whereas iNKT cells displayed subset-specific distribution across eosinophilic and neutrophilic endotypes. In asthma, iNKT cells consistently contributed to disease development in murine models, whereas the roles of MAIT and γδ T cells were controversial, demonstrating both pro- and anti-inflammatory roles depending on anatomical location and disease context. This review summarizes current findings on the contribution of innate T cells to the immunopathology of CRSwNP and asthma and discusses the challenges and future directions in resolving discrepancies arising from methodological and biological variability.