IL-17 Enhances Chemotaxis of Primary Human B Cells during Asthma

Abstract

IL-17 is a pro-inflammatory mediator that is believed to play a critical role in regulating tissue inflammation during asthma, COPD, as well as other inflammatory disorders. The level of expression of IL-17 has been shown to be upregulated in lung bronchial tissue of asthmatic patients. Several reports have provided further evidence that this cytokine could play a key role in enhancing the migration of inflammatory as well as structural cells of the bronchial lung tissue during asthma and COPD. B cell infiltration to sites of inflammation during inflammatory disorders such as bowel disease, asthma and COPD has been reported. Accordingly, in this study we hypothesized that IL-17 may exert a chemotactic effect on primary B cells during asthma. We observed that B cells from asthmatic patients expressed significantly higher levels of IL-17RA and IL-17RC, compared to those of healthy subjects. Using an in-vitro migration assay, B cells were shown to migrate towards both IL-17A and IL-17F. Interestingly, blocking IL-17A and IL-17F signaling using either anti-IL-17R antibodies or MAP kinase inhibitors prevented in vitro migration of B cell towards IL-17. These observations indicate a direct chemotactic effect of IL-17 cytokines on primary peripheral blood B cells with higher effect being on asthmatic B cells. These findings revealed a key role for IL-17 in enhancing the migration of B cells to the lung tissue during asthma or COPD.

Exosomes derived from human adipose mesenchymal stem cells attenuate hypertrophic scar fibrosis by miR-192-5p/IL-17RA/Smad axis

“…IL-17A receptor (IL-17RA) is ubiquitously expressed on many cell types of human body and highly expressed in the bone marrow, thymus, and spleen [ 55 ]. In the airways, IL-17RA is mainly expressed on fibroblasts, epithelial cells, smooth muscle cells, and microvascular endothelial cells [ 21 , 22 ]. However, the effect of IL-17RA on skin fibroblasts has not been elucidated.…”

IL-17A promotes migration and tumor killing capability of B cells in esophageal squamous cell carcinoma

“…In vitro chemotaxis assay demonstrated IL-17A could stimulate the migration of B cells. Similarly, studies in inflammatory lung tissues showed that IL-17A could promote the migration of B cells [ 16 , 17 ]. Several studies have confirmed that B cells could express chemokine receptors CCR2 [ 28 ], CCR6 [ 29 ] and CXCR5 [ 30 ].…”

“…However, there are few reports concerning the effects of IL-17A on the migration and functions of B lymphocytes. Previous studies have demonstrated that IL-17 could recruit B cells in respiratory tissues [ 16 , 17 ]. However, whether IL-17 could promote the recruitment and tumor lysis of B cells in cancer remains unknown.…”

Friend or Foe: The Protective and Pathological Roles of Inducible Bronchus-Associated Lymphoid Tissue in Pulmonary Diseases

“…Early IL-17 is required for protective immunity against the highly pathogenic H5N1 influenza virus infection demonstrated by a mechanism involving induction of CXCL13 and recruitment of CXCR5 + B cells into the lung tissue (31). Accordingly, IL-17 2/2 mice had increased inflammation and decreased total B cells in the lung (19,31), and in vitro, IL-17 axis blockade led to defects in chemotaxis of human B cells (41). These findings suggest that localization and organization of B cells in follicles were likely impaired without IL-17 signaling in these models.…”