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The Effect of α7nAChR Signaling on T Cells and Macrophages and Their Clinical Implication in the Treatment of Rheumatic Diseases

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Abstract

Rheumatoid arthritis (RA) is one of the most common autoimmune disease and until now, the etiology and pathogenesis of RA is not fully understood, although dysregulation of immune cells is one of the leading cause of RA-related pathological changes. Based on current understanding, the priority of anti-rheumatic treatments is to restore immune homeostasis. There are several anti-rheumatic drugs with immunomodulatory effects available nowadays, but most of them have obvious safety or efficacy shortcomings. Therefore, the development of novel anti-rheumatic drugs is still in urgently needed. Cholinergic anti-inflammatory pathway (CAP) has been identified as an important aspect of the so-called neuro-immune regulation feedback, and the interaction between acetylcholine and alpha 7 nicotinic acetylcholine receptor (α7nAChR) serves as the foundation for this signaling. Consistent to its immunomodulatory functions, α7nAChR is extensively expressed by immune cells. Accordingly, CAP activation greatly affects the differentiation and function of α7nAChR-expressing immune cells. As a result, targeting α7nAChR will bring profound therapeutic impacts on the treatment of inflammatory diseases like RA. RA is widely recognized as a CD4+ T cells-driven disease. As a major component of innate immunity, macrophages also significantly contribute to RA-related immune abnormalities. Theoretically, manipulation of CAP in immune cells is a feasible way to treat RA. In this review, we summarized the roles of different T cells and macrophages subsets in the occurrence and progression of RA, and highlighted the immune consequences of CAP activation in these cells under RA circumstances. The in-depth discussion is supposed to inspire the development of novel cell-specific CAP-targeting anti-rheumatic regimens.

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Funding

This work was supported by the Scientific Research Fund for Key Projects of Wannan Medical College (WK2020ZF21), Research project of traditional Chinese Medicine Inheritance and innovation of Anhui Province (2020zcyb02), Scientific Research Project of Anhui Provincial Health Commission (AHWJ2021b038).

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  1. Shu Pan and Yi-Jin Wu contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmacy, The Second Affiliated Hospital of Wannan Medical College, Wuhu, 241000, China

    Shu Pan, Yi-Jin Wu, Sa-Sa Zhang & Qin Yin

  2. School of Pharmacy, Wannan Medical College, Wuhu, 241000, China

    Shu Pan, Yi-Jin Wu, Sa-Sa Zhang & Qin Yin

  3. Research Center of Integration of Traditional Chinese and Western Medicine, Wannan Medical College, Wuhu, 241000, China

    Shu Pan, Yi-Jin Wu & Sa-Sa Zhang

  4. Department of Traditional Chinese Medicine, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital), Wuhu, 241000, China

    Xiu-Ping Cheng & Jian Zuo

  5. Faculty of Traditional Thai Medicine, Prince of Songkla University, Hat Yai, 90110, Thailand

    Opeyemi Joshua Olatunji

  6. Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution, Wannan Medical College, Wuhu, 241000, China

    Jian Zuo

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  1. Shu Pan
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PS wrote the manuscript. ZSS, WYJ and CXP collected the references and participated in the drafting. WYJ, OOJ and ZJ checked, proofread, and polished the manuscript. YQ and ZJ conceived the idea of this work. All authors reviewed and approved the manuscript.

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Correspondence to Qin Yin or Jian Zuo.

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Pan, S., Wu, YJ., Zhang, SS. et al. The Effect of α7nAChR Signaling on T Cells and Macrophages and Their Clinical Implication in the Treatment of Rheumatic Diseases. Neurochem Res 47, 531–544 (2022). https://doi.org/10.1007/s11064-021-03480-1

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