Current understanding of CTLA-4: from mechanism to autoimmune diseases

Md Munnaf Hossen; Yanmei Ma; Zhihua Yin; Yuhao Xia; Jing Du; Jim Yi Huang; Jennifer Jin Huang; Linghua Zou; Zhizhong Ye; Zhong Huang

doi:10.3389/fimmu.2023.1198365

Current understanding of CTLA-4: from mechanism to autoimmune diseases

Front Immunol. 2023 Jul 11:14:1198365. doi: 10.3389/fimmu.2023.1198365. eCollection 2023.

Authors

Md Munnaf Hossen^{1

2

3}, Yanmei Ma^{1

2

3}, Zhihua Yin^{1

3}, Yuhao Xia^{2

4}, Jing Du⁴, Jim Yi Huang⁵, Jennifer Jin Huang⁶, Linghua Zou^{1

7}, Zhizhong Ye^{1

3}, Zhong Huang^{2

3}

Affiliations

¹ Shenzhen Futian Hospital for Rheumatic Diseases, Shenzhen, China.
² Department of Immunology, Biological Therapy Institute, Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Health Science Center, Shenzhen University, Shenzhen, China.
³ Joint Research Laboratory for Rheumatology of Shenzhen University Health Science Center and Shenzhen Futian Hospital for Rheumatic Diseases, Shenzhen, China.
⁴ Department of Laboratory Medicine, Peking University Shenzhen Hospital, Shenzhen, China.
⁵ Department of Psychology, University of Oklahoma, Norman, OK, United States.
⁶ Department of Chemistry and Biochemistry, University of Oklahoma, Norman, OK, United States.
⁷ Department of Rehabilitation Shenzhen Futian Hospital for Rheumatic Diseases, Shenzhen, China.

Abstract

Autoimmune diseases (ADs) are characterized by the production of autoreactive lymphocytes, immune responses to self-antigens, and inflammation in related tissues and organs. Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is majorly expressed in activated T cells and works as a critical regulator in the inflammatory response. In this review, we first describe the structure, expression, and how the signaling pathways of CTLA-4 participate in reducing effector T-cell activity and enhancing the immunomodulatory ability of regulatory T (Treg) cells to reduce immune response, maintain immune homeostasis, and maintain autoimmune silence. We then focused on the correlation between CTLA-4 and different ADs and how this molecule regulates the immune activity of the diseases and inhibits the onset, progression, and pathology of various ADs. Finally, we summarized the current progress of CTLA-4 as a therapeutic target for various ADs.

Keywords: CTLA-4; autoimmune disease; autoimmunity; immune regulation; regulatory T cell.

Publication types

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

MeSH terms

Autoimmune Diseases*
CTLA-4 Antigen
Humans
T-Lymphocytes, Regulatory

Substances

CTLA-4 Antigen
CTLA4 protein, human

Grants and funding

This work was supported by grants from the Shenzhen Science and Technology Basic Research Project JCYJ20190808172005595 and JCYJ20190809151205630, Shenzhen Science and Technology Project JCYJ20180504170414637, Shenzhen Futian Public Welfare Scientific Research Project FTWS2021006 and FTWS2022021, and Sanming Project of Medicine in Shenzhen SZSM201602087.