The Ameliorating Effects of MSCs in Controlling Treg-mediated B-Cell Depletion by Indoleamine 2, 3-dioxygenase Induction in PBMC of SLE Patients


  • Yan Wisnu Prajoko Department of Surgery, Faculty of Medicine, Universitas Diponegoro, Semarang, Indonesia
  • Agung Putra Stem Cell and Cancer Research, Faculty of Medicine, Universitas Islam Sultan Agung, Semarang, Indonesia; Department of Postgraduate Biomedical Science, Faculty of Medicine, Universitas Islam Sultan Agung, Semarang, Indonesia; Department of Pathological Anatomy, Faculty of Medicine, Universitas Islam Sultan Agung, Semarang, Indonesia
  • Bayu Tirta Dirja Department of Microbiology, Faculty of Medicine, Universitas Mataram, Mataram, Indonesia
  • Adi Muradi Muhar Department of Surgery, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia
  • Nur Dina Amalina Stem Cell and Cancer Research, Faculty of Medicine, Universitas Islam Sultan Agung, Semarang, Indonesia; Study Program, Faculty of Mathematics and Natural Sciences, Universitas Negeri Semarang, Semarang, Indonesia



Mesenchymal stem cells, Indoleamine 2, 3-dioxygenase, B cells, T-reg, Systemic lupus erythematosus


BACKGROUND: Mesenchymal stem cells (MSCs) have potent immunosuppressive properties to control systemic lupus erythematosus (SLE) disease by releasing several anti-inflammatory molecules, particularly indoleamine 2, 3-dioxygenase (IDO), and increasing regulatory T cells (Treg) to control innate and adaptive immune cells. However, how MSCs release IDO to modulate Treg in controlling B is poorly understood. Therefore, investigating IDO, Treg, and B cells following MSC administration in SLE is needed.

AIM: This study aimed to investigate the ameliorating effects of MSCs in controlling B cells mediated by an increase of IDO-induced Treg in PBMC of SLE patients.

METHODS: This study used a post-test control group design. MSCs were obtained from human umbilical cord blood and characterized according to their surface antigen expression and multilineage differentiation capacities. PBMCs isolated from SLE patients were divided into five groups: Sham (placebo group), control, and three treatment groups. The treatment groups were treated by coculturing MSCs to PBMCs with a ratio of 1:10, 1:25, and 1:40 for 72 h incubation. Treg and B-cell levels were analyzed by flow cytometry with cytometric bead array (CBA) while the IDO levels were determined by ELISA.

RESULTS: This study showed that the percentages of B cells decreased significantly in groups treated by dose-dependent MSCs, particularly in T1 and T2 groups followed by increased Treg cell percentages. These findings were aligned with the significant increase of the IDO levels.

CONCLUSIONS: MSCs regulated B cells through an increase of IDO-induced Treg in SLE patients’ PBMC.


Download data is not yet available.


Metrics Loading ...

Plum Analytics Artifact Widget Block


Yaniv G, Twig G, Shor DB, Furer A, Sherer Y, Mozes O, et al. A volcanic explosion of autoantibodies in systemic lupus erythematosus: A diversity of 180 different antibodies found in SLE patients. Autoimmun Rev. 2015;14(1):75-9. PMid:25449682 DOI:

Malkiel S, Barlev AN, Atisha-Fregoso Y, Suurmond J, Diamond B. Plasma cell differentiation pathways in systemic lupus erythematosus. Front Immunol. 2018;9:427. PMid:29556239 DOI:

Yap DY, Chan TM. B cell abnormalities in systemic lupus erythematosus and lupus nephritis-role in pathogenesis and effect of immunosuppressive treatments. Int J Mol Sci. 2019;20(24):6231. PMid:31835612 DOI:

Prechl J. A generalized quantitative antibody homeostasis model: Antigen saturation, natural antibodies and a quantitative antibody network. Clin Transl Immunol. 2017;6(2):e131. PMid:28496977 DOI:

Barbado J, Tabera S, Sánchez A, García-Sancho J. Therapeutic potential of allogeneic mesenchymal stromal cells transplantation for lupus nephritis. Lupus. 2018;27(13):2161-5. PMid:30290717 DOI:

Putra A, Ridwan FB, Putridewi AI, Kustiyah AR, Wirastuti K, Sadyah NA, et al. The role of TNF-α _induced MSCs on suppressive inflammation by increasing TGF-β _and IL-10. Open Access Maced J Med Sci. 2018;6(10):1779-83. PMid:30455748 DOI:

Darlan DM, Munir D, Putra A, Jusuf NK. MSCs-released TGFβ1 generate CD4+CD25+Foxp3+ in T-reg cells of human SLE PBMC. J Formos Med Assoc. 2020;120(1):602-8. PMid:32718891 DOI:

Ikhsan R, Putra A, Munir D, Darlan DM, Suntoko B, Kustiyah AR, et al. Mesenchymal stem cells induce regulatory T-cell population in human SLE. BJMS. 2020;19(4):743-8. DOI:

Baghaei K, Hashemi SM, Tokhanbigli S, Asadi Rad A, Assadzadeh-Aghdaei H, Sharifian A, et al. Isolation, differentiation, and characterization of mesenchymal stem cells from human bone marrow. Gastroenterol Hepatol Bed Bench. 2017;10(3):208-13. PMid:29118937

Gebler A, Zabel O, Seliger B. The immunomodulatory capacity of mesenchymal stem cells. Trends Mol Med. 2012;18(2):128-34. PMid:22118960 DOI:

Crop MJ, Baan CC, Korevaar SS, Ijzermans JN, Pescatori M, Stubbs AP, et al. Inflammatory conditions affect gene expression and function of human adipose tissue-derived mesenchymal stem cells. Clin Exp Immunol. 2010;162(3):474-86. PMid:20846162 DOI:

Dorraji SE, Hovd AK, Kanapathippillai P, Bakland G, Eilertsen GØ, Figenschau SL, et al. Mesenchymal stem cells and T cells in the formation of tertiary lymphoid structures in lupus nephritis. Sci Rep. 2018;8(1):7861. PMid:29777158 DOI:

Haddad R, Saldanha-Araujo F. Mechanisms of T-cell immunosuppression by mesenchymal stromal cells: What do we know so far? Biomed Res Int. 2014;2014:216806. PMid:25025040 DOI:

Wu H, Gong J, Liu Y. Indoleamine 2, 3-dioxygenase regulation of immune response (Review). Mol Med Rep. 2018;17(4):4867-73. PMid:29393500 DOI:

Comoli P, Ginevri F, Maccario R, Avanzini MA, Marconi M, Groff A, et al. Human mesenchymal stem cells inhibit antibody production induced in vitro by allostimulation. Nephrol Dial Transplant. 2008;23(4):1196-202. PMid:18029377 DOI:

Shih TA, Roederer M, Nussenzweig MC. Role of antigen receptor affinity in T cell-independent antibody responses in vivo. Nat Immunol. 2002;3(4):399-406. PMid:11896394 DOI:

Lentz VM, Manser T. Cutting edge: Germinal centers can be induced in the absence of T cells. J Immunol. 2001;167(1):15- 20. PMid:11418626 DOI:

Chappell CP, Draves KE, Giltiay NV, Clark EA. Extrafollicular B cell activation by marginal zone dendritic cells drives T cell-dependent antibody responses. J Exp Med. 2012;209(10):1825-40. PMid:22966002 DOI:

Iikuni N, Lourenço EV, Hahn BH, La Cava A. Cutting edge: Regulatory T cells directly suppress B cells in systemic lupus erythematosus. J Immunol. 2009;183(3):1518-22. PMid:19570829 DOI:

Danikowski KM, Jayaraman S, Prabhakar BS. Regulatory T cells in multiple sclerosis and myasthenia gravis. J Neuroinflammation. 2017;14(1):117. PMid:28599652 DOI:

Corcione A, Benvenuto F, Ferretti E, Giunti D, Cappiello V, Cazzanti F, et al. Human mesenchymal stem cells modulate B-cell functions. Blood. 2006;107(1):367-72. PMid:16141348 DOI:

Tabera S, Pérez-Simón JA, Díez-Campelo M, Sánchez-Abarca LI, Blanco B, López A, et al. The effect of mesenchymal stem cells on the viability, proliferation and differentiation of B-lymphocytes. Haematologica. 2008;93(9):1301-9. PMid:18641017 DOI:




How to Cite

Prajoko YW, Putra A, Dirja BT, Muhar AM, Amalina ND. The Ameliorating Effects of MSCs in Controlling Treg-mediated B-Cell Depletion by Indoleamine 2, 3-dioxygenase Induction in PBMC of SLE Patients. Open Access Maced J Med Sci [Internet]. 2022 Jan. 1 [cited 2023 Mar. 31];10(A):6-11. Available from:

Most read articles by the same author(s)

1 2 3 > >>