Altered chromatin landscape in circulating T follicular helper and regulatory cells following grass pollen subcutaneous and sublingual immunotherapy

BackgroundAllergen-specific immunotherapy is a disease-modifying treatment that induces long-term T-cell tolerance.ObjectiveWe sought to evaluate the role of circulating CXCR5+PD-1+ T follicular helper (cTFH) and regulatory (TFR) cells following grass pollen subcutaneous (SCIT) sublingual (SLIT) accompanying changes in their chromatin landscape.MethodsPhenotype function cTFH were initially evaluated pollen-allergic (GPA) group (n = 28) nonatopic healthy controls (NAC, n 13) by mathematical algorithms developed manage high-dimensional data cell culture, respectively. TFR further enumerated NAC 12), GPA 14), SCIT- 10), SLIT- 8) treated groups. Chromatin accessibility was assessed assay for transposase-accessible sequencing (ATAC-seq) investigate epigenetic mechanisms underlying differences between NAC, GPA, SCIT, SLIT groups.ResultscTFH shown be distinct from TH2- TH2A-cell subsets, capable secreting IL-4 IL-21. Both cytokines synergistically promoted B-cell class switching IgE plasma differentiation. Grass allergen induced cTFH-cell proliferation but not (P < .05). higher compared with lower SCIT groups .01). Time-dependent induction IL-4, IL-21, IL-6 observed nasal mucosa intranasal challenge IL-10+ (all, P ATAC-seq analyses revealed differentially accessible regions all groups.ConclusionsFor first time, we showed dysregulation SLIT. Changes landscape allergen-specific cells. Allergen-specific tolerance. We landscape. Phenotype For