Antifibrotics modify B-cell-induced fibroblast migration and activation in patients with idiopathic pulmonary fibrosis

Mohamed F. Ali, Ashley M. Egan, Gaja F. Shaughnessy, Dagny K. Anderson, Theodore J. Kottom, Harika Dasari, Virginia P. Van Keulen, Marie Christine Aubry, Joanne E.S. Yi, Andrew H. Limper, Tobias D Peikert, Eva M. Carmona

Research output: Contribution to journalArticlepeer-review

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. Activation of B-cells by pattern recognition receptors (PRRs) drives the release of inflammatory cytokines, chemokines, and metalloproteases important in the pathophysiology of pulmonary fibrosis. 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 contributes to the inflammatory and profibrotic milieu seen in patients with IPF. B-cell stimulation by CpG and β-glucan via PRRs 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 patients with IPF, and antifibrotics are able to at least partially reverse these responses.

Original languageEnglish (US)
Pages (from-to)722-733
Number of pages12
JournalAmerican journal of respiratory cell and molecular biology
Volume64
Issue number6
DOIs
StatePublished - Jun 2021

Keywords

  • Antifibrotics
  • B-lymphocytes
  • Fibrosis
  • Idiopathic pulmonary fibrosis
  • Pattern recognition receptor

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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