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

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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 summary: Continued allergen exposure drives lung TLO to generate ASCs that home to IL1-instructed para-bronchial cuffs.
Funding Information
  • Research Foundation - Flanders (11D9623N)
  • Research Foundation - Flanders (3F015119)
  • Research Foundation - Flanders (3E011619)
  • Research Foundation - Flanders (3E002820)
  • Research Foundation - Flanders (312ZZR22)
  • Ghent University (bof/baf/2y/2024/01/017)
  • Ghent University (01M01521)
  • Ghent University (01G03524)
  • Ghent University (BOF21-DOC-105)

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