Progenitor T cells drive chronic pulmonary type 2 inflammation.

Type 2 inflammation is coordinated by remarkably durable CD4+ T helper 2 (TH2) cell responses, yet the cellular architecture that drives this chronic inflammation and prevents exhaustion remains poorly understood. To define the TH2 landscape in chronic type 2 inflammation, we established a mouse model of long-term pulmonary allergen exposure, finding that type 2 inflammation was broadly sustained over time and included an expanded T cell factor 1-expressing progenitor-like population. In vivo, lung TH2 progenitors were sufficient to both initiate and sustain type 2 inflammation, coupling self-renewal with effector cell differentiation. Transcriptomic and spatial deconstruction of chronic pulmonary TH2 responses identified interleukin-7 receptor signaling and lung tissue B cell infiltration in the context of tertiary lymphoid structure formation as key factors contributing to the maintenance of TH2 progenitors. Our data define the TH2 progenitor as a distinct cellular state arising during pathogenic chronic type 2 inflammation with a central role in sustaining TH2 responses over time.