Chromatin Landscape of IL-4-expressing CD4 T cells in the lung and lung-draining lymph nodes

Using bulk-, single cell-, ATAC-, and TCR repertoire sequencing, this study reveals that helminth infection causes the expansion of distinct IL-4-competent CD4+ T cells in the lung and lung-draining lymphoid tissues, providing insight into tissue-specific mechanisms of type-2 cytokine regulation and the lineage commitment of T-helper 2 (Th2) and T follicular helper (Tfh) cells. IL-4 competent CD4+ T cells were stratified into three groups: lymphoid-restricted T follicular helper (Tfh) cells; nonlymphoid resident T-helper 2 (Th2) cells; and transitional cells that share identity with both tissue compartments. Differences in transcriptome, locus accessibility, and the enrichment of distinct transcription factor motifs suggested that IL-4 competency was likely achieved via distinct mechanisms among lymphoid- and lung-resident CD4+IL-4+ populations. These findings reveal a complex relationship between lymphoid- and nonlymphoid-resident CD4+ T cell populations in settings of type-2 immunity. Genome-wide ATAC-sequencing was used to profile regulatory regions in 3 distinct CD4+ T cell subsets that arise in lymphoid and nonlymphoid tissues after N. brasiliensis infection.