IL-1 instructs para-bronchial cuff fibroblasts to organize lung antibody secreting cell niches during continued antigen exposure
Lammens, I.; Declercq, J.; Brown, A. S.; Smole, U.; Deswarte, K.; Hoste, E.; Herreman, K.; Sang-aram, C.; Browaeys, R.; Baptista, A. P.; Seurinck, R.; Saeys, Y.; Gevaert, P.; Hammad, H.; Lambrecht, B. N.; Vanhee, S.
Show 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.
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