Experimental study on the regulatory effect of Qinggan Dongyin on T lymphocyte homeostasis in MRL/lpr mice.
Estudio experimental sobre el efecto regulador de Qinggan Dongyin en la homeostasis de los linfocitos T en ratones MRL/lpr.
Keywords:
lupus erythematosus, systemic, Qinggan Dongyin, T-lymphocytes, signal pathways, cGAS-STING protein, mouse
Abstract
Systemic lupus erythematosus (SLE) is an autoimmune disease marked by autoantibody overproduction and increased infection risk, even with current treatments. Dysregulated T lymphocyte homeostasis contributes to SLE progression, prompting exploration of immunomodulatory therapies. This study evaluated the effects of Qinggan Dongyin (QGDY), a compound of traditional Chinese medicine, in a murine SLE model. Twelve female MRL/lpr mice were randomly divided into model and QGDY treatment groups (n=6 each), with age-matched C57BL/6 mice as controls. QGDY (5 mL/kg/day) was administered via gavage for two weeks; controls received saline. Flow cytometry analyzed T cell subsets (CD4+, CD8+, Treg, Th1, Th2, Th17), ELISA measured plasma cytokines (IFN-γ, IL -6, TNF-α, IL -17A, TGF-β), HE staining assessed lung and kidney pathology, and qPCR evaluated cGAS and STING expression. Compared to the model group, QGDY significantly restored T cell balance by increasing CD4+, CD8+, and Treg cells and reducing Th1, Th2, and Th17 cells (p<0.01). QGDY also lowered pro-inflammatory cytokine levels (p<0.05), improved organ histopathology, and normalized elevated cGAS and STING expression (p<0.01). These findings indicate that QGDY exerts immunomodulatory effects in SLE, suggesting therapeutic potential through the regulation of T cell function and inflammatory signalling pathways.
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Singh BK, Singh S. Systemic lupus erythematosus and infections. Reumatismo. 2020;72(3):154-169. https://doi.org/10.4081/reumatismo.2020.1303.
Rao M, Mikdashi J. A Framework to Overcome Challenges in the Management of Infections in Patients with Systemic Lupus Erythematosus. Open Access Rheumatol. 2023; 15:125-137. https://doi.org/10.2147/OARRR.S295036.
Akhlaq A, Aamer S, Hasan KM, Muzammil TS, Sohail AH, Quazi MA, et al. Systemic lupus erythematosus is associated with increased risk of mortality and acute kidney injury in patients with COVID-19 hospitalization: Insights from a National Inpatient Sample analysis. Lupus. 2024;33(3):248-254. https://doi.org/10.1177/09612033241227027.
Solé C, Domingo S, Vidal X, Cortés-Hernández J. Humoral and cellular response in convalescent COVID-19 lupus patients. Sci Rep. 2022;12(1):13787. https://doi.org/10.1038/s41598-022-17334-5.
Rao AP, Patro D. The Intricate Dance of Infections and Autoimmunity: An Interesting Paradox. Indian J Pediatr. 2024;91(9):941- 948. https://doi.org/10.1007/s12098-023-04928-8.
Kang N, Liu X, You X, Sun W, Haneef K, Sun X, Liu W. Aberrant B-Cell Activation in Systemic Lupus Erythematosus. Kidney Dis (Basel). 2022;8(6):437-445. https://doi.org/10.1159/000527213.
Li H, Boulougoura A, Endo Y, Tsokos GC. Abnormalities of T cells in systemic lupus erythematosus: new insights in pathogenesis and therapeutic strategies. J Autoimmun. 2022; 132:102870. https://doi.org/10.1016/j.jaut.2022.102870.
Ding M, Jin L, Zhao J, Yang L, Cui S, Wang X, et al. Add-on sirolimus for the treatment of mild or moderate systemic lupus erythematosus via T lymphocyte sub-sets balance. Lupus Sci Med. 2024;11(1): e001072. https://doi.org/10.1136/lupus- 2023-001072.
Zhang J, Zhang S, Qiao J, Qiu M, Li X. Risk factors analysis and risk assessment model construction of systemic lupus erythematosus patients with infection. Lupus. 2023;32(1):119-128. https://doi.org/10.1177/09612033221141255.
Chen PM, Tsokos GC. The role of CD8+ T-cell systemic lupus erythematosus pathogenesis: an update. Curr Opin Rheumatol 2021;33(6):586-591. https://doi.org/10.1097/BOR.0000000000000815.
Tsai YG, Liao PF, Hsiao KH, Wu HM, Lin CY, Yang KD. Pathogenesis and novel therapeutics of regulatory T cell subsets and interleukin-2 therapy in systemic lupus erythematosus. Front Immunol 2023; 14:1230264. https://doi.org/10.3389/fim mu.2023.1230264.
Talaat RM, Mohamed SF, Bassyouni IH, Raouf AA. Th1/Th2/Th17/Treg cytokine imbalance in systemic lupus erythematosus (SLE) patients: Correlation with disease activity. Cytokine. 2015;72(2):146- 53. https://doi.org/10.1016/j.cyto.2014.12.027
.
Dolff S, Bijl M, Huitema MG, Limburg PC, Kallenberg CG, Abdulahad WH. Disturbed Th1, Th2, Th17 and T(reg) balance in patients with systemic lupus erythematosus. Clin Immunol. 2011;141(2):197-204. https://doi.org/10.1016/j.clim.2011.08.005.
Paquissi FC, Abensur H. The Th17/IL -17 Axis and Kidney Diseases, With Focus on Lupus Nephritis. Front Med (Lausanne). 2021; 8:654912. https://doi.org/10.3389/fmed.2021.654912.
Zan SJ, Wang K, Zhang S, Fu K, Zhou SY, Feng JH, et al. A multicenter cohort study on “Qinggandong Decoction” for prevention of influenza. China J Tradit Chin Med Pharm 2023;38(5):1960-1966.
Sun Y, Geng Q, Zhao Y, Li C, Chen SF. Mechanism of action of Qinggandong decoction in the treatment of influenza based on network pharmacology and molecular docking. Hunan J Tradit Chin Med 2022; 38(01):144-152.
Su R, Lu J, Xi ZN, Wang JB, Song XB, Zhang H, Miao L. Qinggan Dongyin inhibits LPS-induced inflammation of RAW264.7 macrophages by regulating the NF-κB/ iNOS/NO signaling pathway. J Tianjin Univ Tradit Chin Med. 2022;41(06):737-745.
Ren M, Fu K, Zhou SY, Sun X. Expert consensus on clinical application of “Qinggan Yin” series pharmaceutics. Tianjin J Tradi Chin Med. 2020;37(11):1201-1204.
Yuan S, Zeng Y, Li J, Wang C, Li W, He Z, et al. Phenotypical changes and clinical significance of CD4+/CD8+ T cells in SLE. Lupus Sci Med. 2022; 9(1): e000660. https://doi.org/10.1136/lupus-2022-000660.
Schile A, Petrillo M, Vovk A, French R, Leighton K, Dragos Z, et al. A comprehensive phenotyping program for the MRL lpr mouse lupus model. J Immunol. 2018; 200:(1_Supplement):40.2. https://doi.org/10.4049/jimmunol.200.Supp.40.2.
Zhang D, Wang M, Shi G, Pan P, Ji J, Li P. Regulating T Cell Population Alleviates SLE by Inhibiting mTORC1/C2 in MRL/lpr Mice. Front Pharmacol. 2021;11: 579298. https://doi.org/10.3389/fphar.2020.579298.
Contini P, Negrini S, Murdaca G, Borro M, Puppo F. Evaluation of membrane-bound and soluble forms of human leucocyte antigen-G in systemic sclerosis. Clin Exp Immunol. 2018;193(2):152-159. https://doi.org/10.1111/cei.13134.
Hiramatsu-Asano S, Sunahori-Watanabe K, Zeggar S, Katsuyama E, Mukai T, Morita Y, Wada J. Deletion of Mir223 Exacerbates Lupus Nephritis by Targeting S1pr1 in Faslpr/lpr Mice. Front Immunol. 2021;11:616141. https://doi.org/10.3389/fimmu.2020.616141.
Barrett JP, Knoblach SM, Bhattacharya S, Gordish-Dressman H, Stoica BA, Loane DJ. Traumatic Brain Injury Induces cGAS Activation and Type I Interferon Signaling in Aged Mice. Front Immunol. 2021;12:710608. https://doi.org/10.3389/fimmu.2021.710608.
Chuang HC, Chen MH, Chen YM, Yang HY, Ciou YR, Hsueh CH, et al. BPI overexpression suppresses Treg differentiation and induces exosome-mediated inflammation in systemic lupus erythematosus. Theranostics. 2021;11(20):9953-9966. https://doi.org/10.7150/thno.63743.
Sun JK, Zhang WH, Chen WX, Wang X, Mu XW. Effects of early enteral nutrition on Th17/Treg cells and IL -23/IL -17 in septic patients. World J Gastroenterol. 2019;25(22):2799-2808. https://doi.org/10.3748/wjg.v25.i22.2799.
Lourenço JD, Teodoro WR, Barbeiro DF, Velosa APP, Silva LEF, Kohler JB, et al. Th17/Treg-Related Intracellular Signaling in Patients with Chronic Obstructive Pulmonary Disease: Comparison between Local and Systemic Responses. Cells. 2021;10(7):1569. https://doi.org/10.3390/cells10071569.
LiJ,ZhaoJ,ChaiY,LiW,LiuX,ChenY. Astragalus polysaccharide protects sepsis model rats after cecum ligation and puncture. Front Bioeng Biotechnol. 2022;10:1020300. https://doi.org/10.3389/fbioe.2022.1020300.
Published
2025-08-31
How to Cite
Jiang, N., Che, X., Han, H., Xin, H., Wang, S., Li, J., & Zhang, S. (2025). Experimental study on the regulatory effect of Qinggan Dongyin on T lymphocyte homeostasis in MRL/lpr mice.: Estudio experimental sobre el efecto regulador de Qinggan Dongyin en la homeostasis de los linfocitos T en ratones MRL/lpr. Investigación Clínica, 66(3), 269-281. https://doi.org/10.54817/IC.v66n3a04
Section
Original Works
