A unique subset of allergen specific T helper 2 + 17 tissue resident memory cells is established in a mouse model of allergic inflammation 2257678

Abstract

Abstract Introduction Asthma is one of the most common chronic respiratory diseases. Anamnestic inflammation in asthma is sustained by allergen-specific tissue-resident memory (TRM) CD4+ T cells. In addition to the Th2 pathway, components of the Th17 response have been identified as contributors to moderate and severe asthma. Of note, IL-17 — driven airway inflammation is resistant to steroids and to current treatment. A subset of antigen-specific CD4+ memory T cells co-expressing T helper 2 and T helper 17 markers (Th2 + 17 cells) is enriched in individuals with refractory asthma. Methods To investigate TRM2 cell heterogenicity in asthma, a well-established house dust mite (HDM) allergen model in mice was employed and Il13-Cre-mediated lineage-tracing of TRM2 cells was performed. Results Single cell RNA sequencing (scRNAseq) of lineage-labelled Th2-TRMs identified a major TRM2 subpopulation (Gata3+ only) and additional subpopulations that co-expressed specific markers of Th1 (TRM2 + 1), Th17 (TRM2 + 17), and Treg (TRM2+reg) lineages, which reveals significant heterogeneity of allergen-specific, Th2-TRMs in the lung. In addition, recent findings revealed that antigen-specific TRM2 + 17 cells persist in the mouse lungs for up to one year after HDM challenge and are reactivated upon subsequent allergen re-exposure. Conclusion Th2 + 17 TRMs represent a previously uncharacterized population with potential pathogenic relevance in chronic asthma. Follow-up experiments are investigating how genetic background and environmental stimuli influence the regulation and persistence of Th2 + 17 TRMs. By focusing on a novel TRM2 + 17 cell subset implicated in treatment-resistant asthma, our ultimate goal is to elucidate the mechanisms regulating this population to enable the development of effective therapeutics. Funding Source n.a. Topic Categories Immediate Hypersensitivity, Asthma, and Allergic Responses (HYP)