Research Paper Volume 12, Issue 21 pp 21147—21160

Melatonin exerts immunoregulatory effects by balancing peripheral effector and regulatory T helper cells in myasthenia gravis

Ting Chang1, *, , Chunxiao Niu1, *, , Chao Sun1, *, , Ying Ma2, , Rongjing Guo1, , Zhe Ruan1, , Yanwu Gao1, , Xiaodan Lu1, , Huanhuan Li1, , Ye Lin3, , Jiaji Lin4, &, , Zhuyi Li1, &, ,

  • 1 Department of Neurology, Tangdu Hospital, The Air Force Medical University, Xi’an, Shaanxi Province, P.R. China
  • 2 Department of Immunology, The Air Force Medical University, Xi’an, Shaanxi Province, P.R. China
  • 3 Department of Neurology, Chinese PLA General Hospital, Beijing, P.R. China
  • 4 Medical Corp in Unit 93246 of PLA, Changchun, Jilin Province, P.R. China
* Equal contribution

Received: April 23, 2020       Accepted: June 22, 2020       Published: November 2, 2020
How to Cite

Copyright: © 2020 Chang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Myasthenia gravis (MG) is a prototypic organ-specific autoimmune disorder that, in most cases, is mainly mediated by antibodies against the acetylcholine receptor. Evidence implicates CD4+ T helper (Th) cells in the development of MG, whereas regulatory T cells (Tregs) are associated with disease resolution. Melatonin has important immunoregulatory effects in many T cell-mediated autoimmune diseases. However, there are few studies on the role of melatonin in MG. In the present study, we investigated serum melatonin levels and melatonin receptor expression in MG patients and healthy controls (HCs). We also evaluated the impact of melatonin administration on peripheral CD4+ Th cells and related cytokine production. Serum melatonin levels were lower in MG patients than in HCs, and MT1 expression was lower in PBMCs from MG patients than in those from HCs. Administration of melatonin significantly decreased Th1 and Th17 cell responses and proinflammatory cytokine production. Further investigation in vitro revealed that melatonin administration increased FoxP3 and IL-10 expression in CD4+ T cells from MG patients and enhanced the suppressive function of Tregs. These findings indicate that melatonin exerts immunoregulatory activity in MG by balancing effector and regulatory Th cell populations as well as by suppressing proinflammatory cytokine production.


MG: myasthenia gravis; OMG: ocular MG; GMG: generalized MG; QMGS: quantitative MG score; EAMG: experimental autoimmune MG; MS: multiple sclerosis; SLE: systemic lupus erythematosus; EAE: experimental autoimmune encephalomyelitis; Th: T helper; Tfh: follicular Th; Tregs: regulatory T cells; Tresps: responder T cells; HCs: healthy controls; MT: membrane receptor; PBMCs: peripheral blood mononuclear cells; AChR: acetylcholine receptor; NMJ: neuromuscular junction; CD: cluster of differentiation; RT-PCR: reverse transcription-polymerase chain reaction; IL: interleukin; IFNγ: interferon γ; TNFα: tumor necrosis factor α; GM-CSF: granulocyte-macrophage colony stimulating factor; NIST: nonimmunosuppressive therapy; IST: immunosuppressive therapy; FCM: flow cytometry; CAMKIV: calcium/calmodulin-dependent kinase IV; PHA: phytohemagglutinin; ROR: retinoic acid-related orphan receptor; Bcl-6: B cell lymphoma 6; NOD: nonobese diabetic; OD: optical density.