bims-maitce 2025-10-19 papers

Issue of 2025–10–19
two papers selected by
Andy E. Hogan, Maynooth University

Front Immunol. 2025 ;16 1624767

IFNγ regulates MR1 transcription and antigen presentation.

Megan E Huber, Emily A Larson, Taylor N Lust, Chelsea M Heisler, Melanie J Harriff.

Introduction: Antigen presentation molecules play key roles in T cell immunity. Multiple complementary pathways are known to regulate classical MHC-I molecules at transcriptional, translational, and post-translational levels. Intracellular trafficking mechanisms dictating post-transcriptional regulation of MR1, the MHC-I-like molecule which restricts MAIT cells, have been an area of focus; however, little is known about MR1 transcriptional regulation. We demonstrate that interferons regulate MR1 transcription.
Methods: Primary human airway epithelial cells (AEC) were treated with recombinant interferons or co-cultured with MAIT cell clones and antigen sources. MR1 expression was analyzed by RT-qPCR and flow cytometry. MAIT cell activity was quantified by ELISPOT.
Results: Treatment of AECs with IFNβ or IFNγ variably increased MR1 transcripts, while only IFNγ significantly increased surface MR1 expression and enhanced antigen presentation to MAIT cells. The MR1 promoter contains binding motifs for interferon regulatory factor 1 (IRF1), an important MHC-I transcription factor. IRF1 knockout reduced IFNγ-stimulated MR1 transcription, surface expression, and antigen presentation. Conversely, knockout of Nod-like Receptor family CARD domain-containing 5 (NLRC5), a critical component of MHC-I transcription, did not significantly impact MR1 expression. These findings were corroborated with IFNγ-treated primary AEC. MAIT cells in co-culture with Streptococcus pneumoniae-infected AEC produced sufficient IFNγ to stimulate MR1 expression.
Conclusion: Our data support a model where IFNγ from activated MAIT cells or another source stimulates IRF1-dependent MR1 expression and antigen presentation, leading to greater MAIT cell activation. A robust MR1-dependent MAIT cell response may be beneficial for early infection responses, allowing minimal antigen stimulus to generate greater proinflammatory activity.

Keywords: IRF1; MAIT (mucosal-associated invariant T) cell; MR1; airway epithelial cell; interferon-gamma

DOI: https://doi.org/10.3389/fimmu.2025.1624767

Clin Exp Otorhinolaryngol. 2025 Oct 13.

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

Myeong-Seok Lee, Dae Woo Kim, You Jeong Lee.

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.

Keywords: Asthma; CRS; Innate T cells

DOI: https://doi.org/10.21053/ceo.2025-00124