Mucosal Immunity

Recent research has shed light on the plethora of mechanisms by which the gastrointestinal commensal microbiome can influence the local immune response in the gut (in particular, the impact of the immune system on epithelial barrier homeostasis and ensuring microbial diversity).

Immunoglobulin (Ig) A is the most abundant immunoglobulin in humans, and in the airway mucosa secretory IgA (sIgA) plays a pivotal role in first‐line defense against invading pathogens and antigens. IgA has been reported to also have pathogenic effects, including possible worsening of the prognosis of idiopathic pulmonary fibrosis (IPF). However, the precise effects of IgA on lung fibroblasts remain unclear, and we aimed to elucidate how IgA activates human lung fibroblasts. We found that sIgA, but not monomeric IgA (mIgA), induced interleukin (IL)‐6, IL‐8, monocyte chemoattractant protein (MCP)‐1 and Granulocyte Macrophage colony‐stimulating Factor (GM‐CSF) production by normal human lung fibroblasts (NHLFs) at both the protein and mRNA levels. sIgA also promoted proliferation of NHLFs and collagen gel contraction comparable to with transforming growth factor (TGF)‐β, which is involved in fibrogenesis in IPF. Also, Western blot analysis and real‐time quantitative PCR revealed that sIgA enhanced production of α‐smooth muscle actin (α‐SMA) and collagen type I (Col I) by NHLFs. Flow cytometry showed that NHLFs bound sIgA, and among the known IgA receptors, NHLFs significantly expressed CD71 (transferrin receptor). Transfection of siRNA targeting CD71 partially but significantly suppressed cytokine production by NHLFs co‐cultured with sIgA. Our findings suggest that sIgA may promote human lung inflammation and fibrosis by enhancing production of inflammatory or fibrogenic cytokines as well as extracellular matrix, inducing fibroblast differentiation into myofibroblasts and promoting human lung fibroblast proliferation. sIgA's enhancement of cytokine production may be partially due to its binding to CD71 or the secretory component. This article is protected by copyright. All rights reserved.