Mechanism underlying mesenchymal stem cells to regulate autoimmune thrombosis of systemic lupus erythematosus

doi:10.3969/j.issn.2095-4344.2013.45.022

Abstract

Abstract:

BACKGROUND: Systemic lupus erythematosus is a complex autoimmune disease of unknown origin affecting virtually every organ in the human body. It is characterized by abnormal activation of T, B lymphocytes. While aberrant T cells provide help to autoreactive B cells, the autoreactive B cells produce a variety of pathological autoantibodies and immune complex deposition, which could infiltrate the small blood vessels directly or deposit in the vessel wall, thereby causing inflammatory necrosis of the vessel walls. These changes will narrow the vascular lumen, and promote thrombosis, leading to local tissue ischemia and dysfunction. Mesenchymal stem cells can regulate the immune disorders, play an anti-inflammatory role, and repair the immune thrombosis.
OBJECTIVE: To summarize the pathogenesis of immune thrombosis in systemic lupus erythematosus, as well as to introduce the mechanism of mesenchymal stem cell therapy for immunity thrombosis.
METHODS: We searched the PubMed database, Springlink database, ScienceDirect database and HighWire database from January 1990 to June 2013 with the key words of “systemic lupus erythematosus, mesenchymal stem cell, thrombosis, T cells, B cells” in English. An online search of CNKI database, Wanfang database, VIP database from January 1990 to June 2013 was also conducted with the key words of “systemic lupus erythematosus, mesenchymal stem cell, thrombosis, T cells, B cells” in Chinese. A total of 267 literatures were screened out, and 48 documents were included in the review based on the inclusion and exclusion criteria.
RESULTS AND CONCLUSION: Mesenchymal stem cells are multipotential nonhematopoietic progenitor cells capable of multi-directional differentiating into various cell types. Mesenchymal stem cells can suppress T-lymphocyte activation and proliferation, and inhibit secretion of interferon-γ, interleukin-4. Mesenchymal stem cells can also inhibit the proliferation of B cells and the secretion of pathogenic immunoglobulin IgM, IgG, IgA. Thus, mesenchymal stem cells can regulate immune homeostasis and reduce the deposition of autoantibodies and immune complexes, thereby protecting the blood vessels from injury, reducing the secretion of inflammatory cytokines, balancing the coagulation-anticoagulation, and decreasing thrombosis in systemic lupus erythematosus.

Key words: mesenchymal stem cells, lupus erythematosus, systemic, thrombosis, T-Lymphocytes, B-Lymphocytes

CLC Number:

R318

Ren Min-min, Gu Jian. Mechanism underlying mesenchymal stem cells to regulate autoimmune thrombosis of systemic lupus erythematosus[J]. Chinese Journal of Tissue Engineering Research, doi: 10.3969/j.issn.2095-4344.2013.45.022.

Figures/Tables 2

References

[1] Bonfield TL, Nolan Koloze MT, Lennon DP,et al. Defining human mesenchymal stem cell efficacy in vivo. J Inflamm (Lond). 2010 ;7:51.
[2] Moulton VR, Tsokos GC. Abnormalities of T cell signaling in systemic lupus erythematosus. Arthritis Res Ther. 2011;13(2): 207.
[3] Rahman A, Isenberg DA. Systemic lupus erythematosus. N Engl J Med. 2008;358(9):929-939.
[4] Hutloff A, Dittrich AM, Beier KC,et al. ICOS is an inducible T-cell co-stimulator structurally and functionally related to CD28. Nature. 1999;397(6716):263-266.
[5] Simpson TR, Quezada SA, Allison JP. Regulation of CD4 T cell activation and effector function by inducible costimulator (ICOS). Curr Opin Immunol. 2010;22(3):326-332.
[6] Odegard JM, DiPlacido LD, Greenwald L,et al. ICOS controls effector function but not trafficking receptor expression of kidney-infiltrating effector T cells in murine lupus. J Immunol. 2009;182(7):4076-4084.
[7] Garrett-Sinha LA, John S, Gaffen SL. IL-17 and the Th17 lineage in systemic lupus erythematosus. Curr Opin Rheumatol. 2008;20(5):519-525.
[8] Wong CK, Lit LC, Tam LS,et al. Hyperproduction of IL-23 and IL-17 in patients with systemic lupus erythematosus: implications for Th17-mediated inflammation in auto-immunity. Clin Immunol. 2008;127(3):385-393.
[9] Henriques A, Inês L, Pais ML,et al.Th17 cells in systemic lupus erythematosus share functional features with Th17 cells from normal bone marrow and peripheral tissues. Clin Rheumatol. 2012 ;31(3):483-491.
[10] Breitfeld D, Ohl L, Kremmer E,et al. Follicular B helper T cells express CXC chemokine receptor 5, localize to B cell follicles, and support immunoglobulin production. J Exp Med. 2000; 192(11):1545-1552.
[11] Dong W, Zhu P, Wang Y,et al. Follicular helper T cells in systemic lupus erythematosus: a potential therapeutic target. Autoimmun Rev. 2011;10(6):299-304.
[12] Craft JE. Follicular helper T cells in immunity and systemic autoimmunity. Nat Rev Rheumatol. 2012 ;8(6):337-347.
[13] Simpson N, Gatenby PA, Wilson A,et al. Expansion of circulating T cells resembling follicular helper T cells is a fixed phenotype that identifies a subset of severe systemic lupus erythematosus. Arthritis Rheum. 2010;62(1):234-244.
[14] Pierangeli SS, Chen PP, Raschi E,et al. Antiphospholipid antibodies and the antiphospholipid syndrome: pathogenic mechanisms. Semin Thromb Hemost. 2008 ;34(3):236-250.
[15] Pierangeli SS, Chen PP, González EB. Antiphospholipid antibodies and the antiphospholipid syndrome: an update on treatment and pathogenic mechanisms. Curr Opin Hematol. 2006;13(5):366-375.
[16] Mackay F, Figgett WA, Saulep D,et al. B-cell stage and context-dependent requirements for survival signals from BAFF and the B-cell receptor. Immunol Rev. 2010;237(1): 205-225.
[17] Davidson A.The rationale for BAFF inhibition in systemic lupus erythematosus. Curr Rheumatol Rep. 2012;14(4):295- 302.
[18] Ota M, Duong BH, Torkamani A,et al. Regulation of the B cell receptor repertoire and self-reactivity by BAFF. J Immunol. 2010;185(7):4128-4136.
[19] Shirota Y, Yarboro C, Fischer R,et al. Impact of anti-interleukin-6 receptor blockade on circulating T and B cell subsets in patients with systemic lupus erythematosus. Ann Rheum Dis. 2013;72(1):118-128.
[20] Kyttaris VC, Tsokos GC.Targeting lymphocyte signaling pathways as a therapeutic approach to systemic lupus erythematosus. Curr Opin Rheumatol. 2011;23(5):449-453.
[21] Chung SW, Park JW, Lee SA,et al. Thrombin promotes proinflammatory phenotype in human vascular smooth muscle cell. Biochem Biophys Res Commun. 2010;396(3): 748-754.
[22] Yuan W, DiMartino SJ, Redecha PB,et al. Systemic lupus erythematosus monocytes are less responsive to interleukin-10 in the presence of immune complexes. Arthritis Rheum. 2011;63(1):212-218.
[23] Weckerle CE, Mangale D, Franek BS,et al. Large-scale analysis of tumor necrosis factor α levels in systemic lupus erythematosus. Arthritis Rheum. 2012;64(9):2947-2952.
[24] Shirinsky I, Polovnikova O, Kalinovskaya N,et al. The effects of fenofibrate on inflammation and cardiovascular markers in patients with active rheumatoid arthritis: a pilot study. Rheumatol Int. 2012. [Epub ahead of print]
[25] Soleymaninejadian E, Pramanik K, Samadian E. Immunomodulatory properties of mesenchymal stem cells: cytokines and factors. Am J Reprod Immunol. 2012;67(1): 1-8.
[26] 张培培,刘慧纯,王世民,等.脑缺血再灌注损伤大鼠尾静脉移植脐带间充质干细胞的安全性[J].中国组织工程研究,2012,16(14): 2581-2584.
[27] Salem HK, Thiemermann C. Mesenchymal stromal cells: current understanding and clinical status. Stem Cells. 2010; 28(3):585-596.
[28] Mariño E, Grey ST. B cells as effectors and regulators of autoimmunity. Autoimmunity. 2012;45(5):377-387.
[29] Traggiai E, Volpi S, Schena F,et al. Bone marrow-derived mesenchymal stem cells induce both polyclonal expansion and differentiation of B cells isolated from healthy donors and systemic lupus erythematosus patients. Stem Cells. 2008; 26(2):562-569.
[30] Asari S, Itakura S, Ferreri K,et al. Mesenchymal stem cells suppress B-cell terminal differentiation. Exp Hematol. 2009; 37(5):604-615.
[31] Schena F, Gambini C, Gregorio A,et al. Interferon-γ- dependent inhibition of B cell activation by bone marrow-derived mesenchymal stem cells in a murine model of systemic lupus erythematosus. Arthritis Rheum. 2010; 62(9):2776-2786.
[32] Asari S, Itakura S, Ferreri K,et al. Mesenchymal stem cells suppress B-cell terminal differentiation. Exp Hematol. 2009; 37(5):604-615.
[33] Ma X, Che N, Gu Z,et al. Allogenic mesenchymal stem cell transplantation ameliorates nephritis in lupus mice via inhibition of B-cell activation. Cell Transplant. 2012. [Epub ahead of print]
[34] Najar M, Raicevic G, Boufker HI,et al. Mesenchymal stromal cells use PGE2 to modulate activation and proliferation of lymphocyte subsets: Combined comparison of adipose tissue, Wharton's Jelly and bone marrow sources. Cell Immunol. 2010;264(2):171-179.
[35] Yagi H, Soto-Gutierrez A, Parekkadan B,et al. Mesenchymal stem cells: Mechanisms of immunomodulation and homing. Cell Transplant. 2010;19(6):667-679.
[36] Fu QL, Chow YY, Sun SJ,et al. Mesenchymal stem cells derived from human induced pluripotent stem cells modulate T-cell phenotypes in allergic rhinitis. Allergy. 2012;67(10): 1215-1222.
[37] Sun YQ, Deng MX, He J,et al. Human pluripotent stem cell-derived mesenchymal stem cells prevent allergic airway inflammation in mice. Stem Cells. 2012;30(12):2692-2699.
[38] Hemeda H, Jakob M, Ludwig AK,et al. Interferon-gamma and tumor necrosis factor-alpha differentially affect cytokine expression and migration properties of mesenchymal stem cells. Stem Cells Dev. 2010;19(5):693-706.
[39] Yang SH, Park MJ, Yoon IH,et al. Soluble mediators from mesenchymal stem cells suppress T cell proliferation by inducing IL-10. Exp Mol Med. 2009;41(5):315-324.
[40] Yagi H, Soto-Gutierrez A, Parekkadan B,et al. Mesenchymal stem cells: Mechanisms of immunomodulation and homing. Cell Transplant. 2010;19(6):667-679.
[41] English K.Mechanisms of mesenchymal stromal cell immunomodulation.Immunol Cell Biol. 2013;91(1):19-26.
[42] Duffy MM, Pindjakova J, Hanley SA,et al. Mesenchymal stem cell inhibition of T-helper 17 cell- differentiation is triggered by cell-cell contact and mediated by prostaglandin E2 via the EP4 receptor. Eur J Immunol. 2011;41(10):2840-2851.
[43] Griffin MD, Ritter T, Mahon BP. Immunological aspects of allogeneic mesenchymal stem cell therapies. Hum Gene Ther. 2010;21(12):1641-1655.
[44] Sun L, Akiyama K, Zhang H,et al. Mesenchymal stem cell transplantation reverses multiorgan dysfunction in systemic lupus erythematosus mice and humans.Stem Cells. 2009; 27(6):1421-1432.
[45] Choi H, Lee RH, Bazhanov N,et al. Anti-inflammatory protein TSG-6 secreted by activated MSCs attenuates zymosan-induced mouse peritonitis by decreasing TLR2/NF-κB signaling in resident macrophages. Blood. 2011; 118(2):330-338.
[46] François M, Romieu-Mourez R, Li M,et al. Human MSC suppression correlates with cytokine induction of indoleamine 2,3-dioxygenase and bystander M2 macrophage differentiation. Mol Ther. 2012;20(1):187-195.
[47] Zhang QZ, Su WR, Shi SH,et al. Human gingiva-derived mesenchymal stem cells elicit polarization of m2 macrophages and enhance cutaneous wound healing. Stem Cells. 2010;28(10):1856-1868.
[48] Ylöstalo JH, Bartosh TJ, Coble K,et al. Human mesenchymal stem/stromal cells cultured as spheroids are self-activated to produce prostaglandin E2 that directs stimulated macrophages into an anti-inflammatory phenotype. Stem Cells. 2012;30(10):2283-2296.