The Role of Innate T Cells in Inflammatory Disorders in Asthma and Chronic Rhinosinusitis.

Abstract

Chronic rhinosinusitis (CRS) and asthma frequently coexist and represent heterogeneous inflammatory disorders of the upper and lower airways, respectively. Type 2 inflammation, mediated by eosinophils and CD4 T cells, has long been recognized as a central driver of both CRS with nasal polyps (CRSwNP) and asthma pathogenesis. However, emerging evidence underscores the critical roles of innate T cells, such as invariant natural killer T (iNKT), mucosal-associated invariant T (MAIT), and γδ T cells, in airway inflammatory diseases. These innate T cells are enriched in sinonasal tissues and contribute to mucosal inflammation through cytokine production, exhibiting functional polarization that reflects local inflammatory cues. In particular, MAIT17 and Vγ1⁺ γδ T cells have been associated with tissue eosinophilia and disease severity in patients with eosinophilic CRSwNP, whereas iNKT cells display subset-specific distributions across eosinophilic and neutrophilic endotypes. In asthma, iNKT cells consistently contribute to disease development in murine models, whereas the functions of MAIT and γδ T cells remain controversial, showing both pro- and anti-inflammatory effects depending on anatomical location and disease context. This review summarizes current evidence on the contribution of innate T cells to the immunopathology of CRSwNP and asthma and discusses the challenges and future directions in reconciling discrepancies arising from methodological and biological variability.