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HIF-1α+ CD4 T cells coordinate a tissue resident immune cell network in the lung [scRNA-seq]

GSE291400 Mus musculus Expression profiling by high throughput sequencing; Other 8 samples Submitted 2026/02/25 Platform GPL24247
Summary
Pulmonary infection leads to the development of CD4+ T resident helper (TRH) cells in the lung. TRH cells generated after influenza infection support local humoral responses and exhibit differentiation plasticity following infectious challenge. A subset of TRH cells is enriched for expression of the transcription factor HIF-1α which has unknown function in the lung. Here we find that inducible deletion of HIF-1α in CD4 T cells leads to decreased numbers of CXCR6+ tissue resident T cells with minimal impact on peripheral lymphoid responses. At the same time, HIF-1α deletion impairs the replenishment of tissue resident macrophages and NK cells, as well as influenza specific IgA titers. These seemingly disparate responses converge upon a requirement for IL-21 produced by HIF-1α+ CD4 T cells. A similar HIF-1α dependent network is engaged in a lung adenocarcinoma model, highlighting novel roles for HIF-1α+ CD4 T cells in coordinating protective immunity during infection and cancer.
Published in
HIF-1α(+) CD4(+) T cells coordinate a tissue-resident immune cell network in the lung
de Lima J, Swarnalekha N, Depew CE et al. · Immunity 2026 · PMID 41794032 · doi:10.1016/j.immuni.2026.01.023
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Also filed as BioProject PRJNA1233295 and SRA study SRP568720. Searching any of these in the dataset finder brings you back here.

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