Journal
INTERNATIONAL IMMUNOPHARMACOLOGY
Volume 93, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.intimp.2021.107434
Keywords
Leflunomide; Experimental autoimmune myasthenia gravis; Humoral immune response; Cellular immune response
Categories
Funding
- National Natural Science Foundation of China [81873772, 81971754]
- National Natural Science Foundation Key International (Regional) Cooperation Research Project [81620108010]
- Clinical Study of 5010 Planned Project Sun Yatsen University [2010003]
- Science and Technology Planned Project of Guangdong in China [2007B16002039]
- National Key Clinical Department and Key Discipline of Neurology, Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases [2014B030301035]
- Southern China International Cooperation Base for Early Intervention and Functional Rehabilitation of Neurological Diseases [2015B050501003]
- Guangdong Provincial Engineering Center for Major Neurological Disease Treatment
- Guangdong Provincial Translational Medicine Innovation Platform for Diagnosis and Treatment of Major Neurological Disease
- Guangdong Provincial Clinical Research Center for Neurological Diseases
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The study found that leflunomide can alleviate the severity of EAMG by regulating humoral immune responses and balancing Th cell subsets, potentially by inhibiting Tfh cells and reducing antibody secretion.
Leflunomide, an immunosuppressive disease-modifying anti-rheumatic drug (DMARD), is widely used in the treatment of rheumatoid arthritis (RA), psoriatic arthritis (PA) as well as multiple sclerosis. However, its role in myasthenia gravis (MG) has not yet been clearly explored. Here, we investigated the effect of leflunomide on experimental autoimmune myasthenia gravis (EAMG) in vivo and in vitro. The results demonstrated that leflunomide alleviated the severity of EAMG associated with reduced serum total anti-acetylcholine receptor (AChR) IgG levels. During the development of EAMG, the increase of follicular helper T cells (Tfh) 1, Tfh 17 cells and decrease of follicular regulatory T cells (Tfr) were reversely altered after leflunomide administration. Our work further found that leflunomide might inhibit Tfh cells through the IL-21/STAT3 pathway to reduce the secretion of antibodies by B cells. In addition, leflunomide rebuilt the balance of Th1/Th2/Th17/Treg subsets. These results suggested that leflunomide ameliorated EAMG severity by regulating humoral immune responses and Th cell profiles thereby providing a novel effective treatment strategy for MG.
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