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Antifibrotics Modify B-cell Induced Fibroblast Migration and Activation in IPF Patients.

Mohamed F. Ali,A. Egan,G. Shaughnessy,D. Anderson,T. Kottom,H. Dasari,V. V. Van Keulen,M. Aubry,E. Yi,A. Limper,T. Peikert,E. Carmona

Published 2021 in American Journal of Respiratory Cell and Molecular Biology

ABSTRACT

B-cell activation is increasingly linked to numerous fibrotic lung diseases and it is well-known that aggregates of lymphocytes form in the lung of many of these patients (1, 2). Activation of B-cells by pattern recognition receptors (PRR) drives the release of inflammatory cytokines, chemokines and metalloproteases important in the pathophysiology of pulmonary fibrosis (3-6). However, the specific mechanisms of B-cell activation in patients with idiopathic pulmonary fibrosis (IPF) are poorly understood. Herein, we have demonstrated that B-cell activation by microbial antigens contribute to the inflammatory and pro-fibrotic milieu seen in IPF patients. B-cell stimulation by CpG and β-glucan via PRR resulted in activation of mTOR-dependent and independent pathways. Moreover, we showed that the B-cell secreted inflammatory milieu is specific to the inducing antigen and causes differential fibroblast migration and activation. B-cell responses to infectious agents and subsequent B-cell-mediated fibroblast activation are modifiable by antifibrotics but each seems to exert a specific and different effect. These results suggest that upon PRR activation by microbial antigens, B-cells can contribute to the inflammatory and fibrotic changes seen in IPF patients and antifibrotics are able to at least partially reverse these responses.

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