Damage-induced NAD release activates intestinal CD4+ and CD8+ T cell via P2X7R signaling

Fandi Bu; Shiyang Huang; Xiaobao Yang; Luyang Wei; Dong Zhang; Zhongtao Zhang; Dan Tian

doi:10.1016/j.cellimm.2023.104677

Damage-induced NAD release activates intestinal CD4+ and CD8+ T cell via P2X7R signaling

Cell Immunol. 2023 Mar:385:104677. doi: 10.1016/j.cellimm.2023.104677. Epub 2023 Feb 2.

Authors

Fandi Bu¹, Shiyang Huang², Xiaobao Yang¹, Luyang Wei¹, Dong Zhang³, Zhongtao Zhang⁴, Dan Tian⁵

Affiliations

¹ Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
² Beijing Key Laboratory of Tolerance Induction and Organ Protection in Transplantation, Beijing, China; Immunology Research Center for Oral and Systemic Health, Beijing Friendship Hospital, Capital Medical University, Beijing, China; Beijing Clinical Research Institute, Beijing, China.
³ Beijing Key Laboratory of Tolerance Induction and Organ Protection in Transplantation, Beijing, China; Immunology Research Center for Oral and Systemic Health, Beijing Friendship Hospital, Capital Medical University, Beijing, China; Beijing Clinical Research Institute, Beijing, China; National Clinical Research Center for Digestive Diseases, Beijing, China.
⁴ Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China; Beijing Clinical Research Institute, Beijing, China; National Clinical Research Center for Digestive Diseases, Beijing, China. Electronic address: zhangzht@ccmu.edu.cn.
⁵ Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China; Beijing Key Laboratory of Tolerance Induction and Organ Protection in Transplantation, Beijing, China; Immunology Research Center for Oral and Systemic Health, Beijing Friendship Hospital, Capital Medical University, Beijing, China; National Clinical Research Center for Digestive Diseases, Beijing, China. Electronic address: tiand@ccmu.edu.cn.

PMID: 36746070
DOI: 10.1016/j.cellimm.2023.104677

Abstract

Background: Postoperative ileus (POI) is characterized by the activation of inflammation triggered by tissue damage. Damage-associated molecular patterns (DAMPs) reportedly induce local inflammation after injury. However, the impact of DAMPs on intestinal resident lymphocytes during POI remains poorly elucidated.

Methods: POI in mice was induced via intestinal manipulation (IM). The concentration of nicotinamide adenine dinucleotide (NAD) was detected after IM. The gastrointestinal motility of the mice was assessed after IM or NAD injection. Cytokine production and calcium influx in T cells were investigated after NAD stimulation using flow cytometry.

Results: The concentration of extracellular NAD significantly increased after IM administration, and NAD directly impaired gastrointestinal motility. Intraperitoneal injection of NAD promoted the expression of TNF-α in intestinal CD8+ and CD4+ T cells, but only IFN-γ production by CD8+ T cells was significantly promoted by NAD injection. Granzyme B production in CD8+ and CD4+ T cells decreased after administration. Concordantly, the same results were observed in NAD stimulation of intestinal CD3+ T cells in vitro. Blocking the P2X7R-related membrane enzyme ART2.2 significantly diminished the pro-inflammatory effect of NAD.

Conclusion: IM includes the release of NAD derived from damaged tissues, consequently promoting pro-inflammatory cytokine production in intestinal CD4+ and CD8+ T lymphocytes. NAD-induced intestinal T cells activation may be associated with POI progression in the mouse.

Keywords: Inflammation; Intestinal T cells; Nicotinamide adenine dinucleotide; Postoperative ileus.

Publication types

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

MeSH terms

Animals
CD4-Positive T-Lymphocytes / metabolism
CD8-Positive T-Lymphocytes / metabolism
Cytokines
Ileus* / metabolism
Inflammation / metabolism
Mice
NAD*
Postoperative Complications / metabolism

Substances

NAD
Cytokines