Semaphorin 7A is protective during inflammatory peritonitis through integrin receptor signaling

Andreas Körner; David Köhler; Mariella Schneider; Judith M Roth; Tiago F Granja; Claudia Eggstein; Valbona Mirakaj; Peter Rosenberger

doi:10.3389/fimmu.2023.1251026

Semaphorin 7A is protective during inflammatory peritonitis through integrin receptor signaling

Front Immunol. 2023 Nov 29:14:1251026. doi: 10.3389/fimmu.2023.1251026. eCollection 2023.

Authors

Andreas Körner¹, David Köhler¹, Mariella Schneider², Judith M Roth¹, Tiago F Granja³, Claudia Eggstein¹, Valbona Mirakaj¹, Peter Rosenberger¹

Affiliations

¹ Department of Anesthesiology and Intensive Care Medicine, University Hospital, Tübingen, Germany.
² Department of Obstetrics and Gynecology, Augsburg University Hospital, Augsburg, Germany.
³ CBIOS-Universidade Research Center for Biosciences & Health Technologies, Universidade Lusófona, Lisbon, Portugal.

Abstract

Introduction: The study explores the role of endothelial Semaphorin 7A (SEMA7A) in inflammatory processes. SEMA7A is known for enhancing inflammation during tissue hypoxia and exhibiting anti-inflammatory properties in the intestinal system during colitis. This research extends the understanding of SEMA7A's function by examining its role in inflammatory peritonitis and intestinal inflammation.

Methods: The research involved inducing peritonitis in SEMA7A knockout (SEMA7A^-/-) and wild-type (WT) animals through Zymosan A (ZyA) injection. The inflammatory response was assessed by measuring cell count and cytokine release. In parallel, the study investigated the expression of SEMA7A in intestinal epithelial cells under inflammatory stimuli and its impact on interleukin 10 (IL-10) production using an in vitro co-culture model of monocytes and epithelial cells. Additionally, the distribution of SEMA7A target receptors, particularly ITGAV/ITGB1 (CD51/CD29), was analyzed in WT animals.

Results: The results revealed that SEMA7A^-/- animals exhibited increased inflammatory peritonitis compared to the WT animals. Inflammatory conditions in intestinal epithelial cells led to the induction of SEMA7A. The co-culture experiments demonstrated that SEMA7A induced IL-10 production, which depended on integrin receptors and was independent of PLXNC1 expression. Furthermore, ITGAV/ITGB1 emerged as the predominant SEMA7A receptor in the intestinal area of WT animals.

Discussion: These findings underscore the multifaceted role of SEMA7A in inflammatory processes. The differential responses in peritonitis and intestinal inflammation suggest that SEMA7A's function is significantly influenced by the expression and distribution of its target receptors within different organ systems. The study highlights the complex and context-dependent nature of SEMA7A in mediating inflammatory responses.

Keywords: SEMA7A; inflammation; integrin; neuronal guidance cues; peritonitis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antigens, CD / metabolism
Inflammation
Integrins
Interleukin-10 / genetics
Peritonitis* / chemically induced
Semaphorins* / genetics
Semaphorins* / metabolism

Substances

Antigens, CD
Integrins
Interleukin-10
Semaphorins

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the grants from the Deutsche Forschungs-gemeinschaft, DFG-KO 6563/1-1 (to AK), the grant DFG-RO 3671/14-1 (to PR) and the grant DFG-MI 1506/4-2 (to VM).