Staphylococcal superantigen‐like protein 3 triggers murine mast cell adhesion by binding to CD43 and augments mast cell activation

Author:

Kawano Sae1,Noda Chisaki1,Itoh Saotomo1ORCID,Urabe Ayaka1,Fujii Chifumi234,Ogawa Isamu1,Suzuki Ryo5ORCID,Hida Shigeaki1ORCID

Affiliation:

1. Department of Molecular and Cellular Health Sciences, Graduate School of Pharmaceutical Sciences Nagoya City University Nagoya Aichi Prefecture Japan

2. Department of Biotechnology Institute for Biomedical Sciences, Shinshu University Matsumoto Nagano Prefecture Japan

3. Department of Molecular Pathology Shinshu University School of Medicine Matsumoto Nagano Prefecture Japan

4. Center for Medical Education and Clinical Training Shinshu University School of Medicine Matsumoto Nagano Prefecture Japan

5. Laboratory of Hygienic Chemistry, Faculty of Pharmaceutical Science Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University Kanazawa Ishikawa Prefecture Japan

Abstract

AbstractStaphylococcus aureus is a noteworthy pathogen in allergic diseases, as four staphylococcal exotoxins activate mast cells, a significant contributor to inflammation, in an IgE‐independent manner. Although the adhesion of mast cells is an essential process for their immune responses, only a small number of exotoxins have been reported to affect the process. Here, we demonstrated that staphylococcal superantigen‐like (SSL) 3, previously identified as a toll‐like receptor 2 agonist, induced the adhesion of murine bone marrow‐derived mast cells to culture substratum. SSL3‐induced adhesion was mediated by fibronectin in an Arg‐Gly‐Asp (RGD) sequence‐dependent manner, suggesting the integrins were involved in the process. Additionally, SSL3 was found to bind to an anti‐adhesive surface protein CD43. SSL3 induced the adhesion of HEK293 cells expressing exogenous CD43, suggesting that CD43 is the target molecule for adhesion induced by SSL3. Evaluation of SSL3‐derived mutants showed that the C‐terminal region (253–326), specifically T285 and H307, are necessary to induce adhesion. SSL3 augmented the IL‐13 production of mast cells in response to immunocomplex and SSL12. These findings reveal a novel function of SSL3, triggering cell adhesion and enhancing mast cell activation. This study would clarify the correlation between S. aureus and allergic diseases such as atopic dermatitis.

Funder

SENSHIN Medical Research Foundation

Takeda Science Foundation

Publisher

Wiley

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