The plexin C1 receptor promotes acute inflammation

Abstract

Acute inflammation is the pathophysiological basis of important clinical conditions associated with organ failure. The initial inflammatory response is controlled by the chemokine system, yet recent data have indicated that the neuronal guidance cues are significantly involved in the orchestration of this process. Previous work has shown the proinflammatory capacity of the guidance cue semaphorin (Sema) 7a, but the role of one of its target receptors, the plexin C1 (PLXNC1) receptor is to date unknown. We report here that PLXNC1 is expressed outside the nervous system and induced during acute inflammation.

Semaphorin 7A plays a critical role in IgE-mediated airway inflammation in mice

“…It has been reported that the inflammatory cells including macrophages, lymphocytes, and eosinophils express PLXNC1 (Esnault et al, 2014;Konig et al, 2014), suggesting that SEMA7A contributes to the infiltration by not only neutrophils but also macrophages, lymphocytes, and eosinophils in the lungs of IgE-sensitized mice. However, in the airway inflammation by the coadministration of IL-33 and IL-17A, the treatment with anti-SEMA7A antibody did not suppress the infiltration by macrophages and lymphocytes in BALF, although neutrophils and eosinophils were inhibited.…”

Differential expression of sema3A and sema7A in a murine model of multiple sclerosis: Implications for a therapeutic design

“…PLXN-C1 is known to bind to sema7A and has been described as a functional receptor of this semaphorin in different cell types, although the relevance of PLNX-C1 in immune processes has recently been associated to acute inflammation, most likely influencing granulocyte function [53]. In addition, in the immune system α1β1-integrin is a predominant receptor for sema7A, being involved in the formation of the immune synapse between macrophages and T-cells [34].…”

Immunomodulatory Functions of Neuronal Guidance Proteins

“…Subsequent work showed that Sema7A is expressed on the surface of endothelial cells and increases the infiltration of neutrophils during tissue hypoxia [37]. This is likely mediated, at least in part, through the Plexin C1 receptor ( Figure [ Plexin C1 itself propagates the infiltration of immune cells into sites of sterile pulmonary inflammation and also during Zymosan A-induced inflammation [38,39]. By contrast, Sema7A was also found to be protective during dextran sulfate sodium (DSS)-induced colitis, where it increased the production of the anti-inflammatory cytokine IL-10 through the anb1 integrin receptor [40].…”