IL-1 instructs para-bronchial cuff fibroblasts to organize lung antibody secreting cell niches during continued antigen exposure

Abstract

Secondary lymphoid organs (SLO) are prototypic sites of antibody production, yet mucosal sites also generate and maintain mucosal antibodies during continued inflammation. Using a murine model of house dust mite-induced airway inflammation, we show that prolonged allergen exposure induces tertiary lymphoid organs (TLO) within para-bronchial adventitial cuffs. Within these regions, IL-1 signaling instructs fibroblasts to form niches that recruit, retain, and sustain lung antibody-secreting cells (ASCs) through chemokine induction. These mucosal ASCs share immunoglobulin repertoires with TLO-derived germinal center B cells. Thus, continued allergen exposure reshapes the lung microenvironment by converting para-bronchial fibroblasts into IL-1-dependent supportive niches for non-IgE antibody production, revealing a fibroblast-mediated mechanism for local immune regulation in chronic inflammation. One sentence summaryContinued allergen exposure drives lung TLO to generate ASCs that home to IL1-instructed para-bronchial cuffs.