Abstract
Background
T cell-mediated inflammation plays an important role in the development of psoriasis. Mesenchymal stem cells (MSCs) are a population of multipotent cells that regulate the T cell-mediated immune response.
Objectives
To investigate the effects of psoriatic dermal mesenchymal stem cells (p-DMSCs) on proliferation, apoptosis and differentiation of T cells.
Materials & Methods
p-DMSCs and normal DMSCs (n-DMSCs) were isolated from psoriatic skin and normal healthy controls, respectively, and co-cultured with activated T cells isolated from healthy volunteers using a Transwell system. Proliferation and apoptosis of T cells were assessed by cell count and flow cytometry, respectively. Expression levels of transcription factors associated with subtypes of T cells and cytokines were measured by qRT-PCR and western blot.
Results
Both p-DMSCs and n-DMSCs inhibited T cell proliferation and cytokine production. Similarly, the presence of p-DMSCs and n-DMSCs decreased the expression levels of both T-bet and ROR-γt in T cells. However, n-DMSCs exhibited a stronger inhibitory effect than p-DMSCs on T cell proliferation, cytokine production, and T-bet and ROR-γt expression.
Conclusion
These results suggest that the effect of p-DMSCs on T cell function could contribute, at least in part, to the pathogenesis of psoriasis.
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References
Zhang K, Li X, Yin G, Liu Y, Tang X. Functional characterization of T cells differentiated in vitro from bone marrow-derived CD34 cells of psoriatic patients with family history. Exp Dermatol 2010; 19: e128–35.
Li X, Li J, Yang Y, et al. Differential gene expression in peripheral blood T cells from patients with psoriasis, lichen planus, and atopic dermatitis. J Am Acad Dermatol 2013; 69: e23543.
Lowes MA, Kikuchi T, Fuentes-Duculan J, et al. Psoriasis vulgaris lesions contain discrete populations of Th1 and Th17 T cells. J Invest Dermatol 2008; 128: 1207–11.
Luz-Crawford P, Espinosa-Carrasco G, Ipseiz N, et al. Gilz-Activin a as a novel signaling axis orchestrating mesenchymal stem cell and Th17 cell interplay. Theranostics 2018; 8: 846–59.
Aggarwal S, Pittenger MF. Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood 2005; 105: 1815–22.
Liu R, Wang Y, Zhao X, Yang Y, Zhang K. Lymphocyte inhibition is compromised in mesenchymal stem cells from psoriatic skin. Eur J Dermatol 2014; 24: 560–7.
Mohanty A, Polisetti N, Vemuganti GK. Immunomodulatory properties of bone marrow mesenchymal stem cells. J Biosci 2020: 45.
Wang Y, Chen X, Cao W, Shi Y. Plasticity of mesenchymal stem cells in immunomodulation: pathological and therapeutic implications. Nat Immunol 2014; 15: 1009–16.
Zhou F, Zhu Z, Gao J, et al. NFKB1 mediates Th1/Th17 activation in the pathogenesis of psoriasis. Cell Immunol 2018; 331: 16–21.
Szabo SJ, Kim ST, Costa GL, Zhang X, Fathman CG, Glimcher LH. A novel transcription factor, T-bet, directs Th1 lineage commitment. Cell 2000; 100: 655–69.
Ivanov II, McKenzie BS, Zhou L, et al. The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell 2006; 126: 1 121–33.
Kim J, Krueger JG. The immunopathogenesis of psoriasis. Dermatol Clin 2015; 33: 13–23.
Castro-Manrreza ME, Bonifaz L, Castro-Escamilla O, et al. Mesenchymal stromal cells from the epidermis and dermis of psoriasis patients: morphology, immunophenotype, differentiation patterns, and regulation of T cell proliferation. Stem Cells Int 2019; 2019: 4541797.
Maddur MS, Miossec P, Kaveri SV, Bayry J. Th17 cells: biology, pathogenesis of autoimmune and inflammatory diseases, and therapeutic strategies. Am J Pathol 2012; 181: 8–18.
Chang HW, Yan D, Singh R, et al. Alteration of the cutaneous microbiome in psoriasis and potential role in Th17 polarization. Microbiome 2018; 6: 154.
Yang XO, Pappu BP, Nurieva R, et al. T helper 17 lineage differentiation is programmed by orphan nuclear receptors ROR alpha and ROR gamma. Immunity 2008; 28: 29–39.
Lazarevic V, Glimcher LH, Lord GM. T-bet: a bridge between innate and adaptive immunity. Nat Rev Immunol 2013; 13: 777–89.
Tang L, Yang X, Liang Y, Xie H, Dai Z, Zheng G. Transcription factor retinoid-related orphan receptor gammat: a promising target for the treatment of psoriasis. Front Immunol 2018; 9: 1210.
Skepner J, Ramesh R, Trocha M, et al. Pharmacologic inhibition of RORgammat regulates Th17 signature gene expression and suppresses cutaneous inflammation in vivo. J Immunol 2014; 192: 2564–75.
Ghannam S, Pene J, Moquet-Torcy G, Jorgensen C, Yssel H. Mesenchymal stem cells inhibit human Th17 cell differentiation and function and induce a T regulatory cell phenotype. J Immunol 2010; 185: 302–12.
Choi EW, Lee M, Song JW, Shin IS, Kim SJ. Mesenchymal stem cell transplantation can restore lupus disease-associated miRNA expression and Th1/Th2 ratios in a murine model of SLE. Sci Rep 2016; 6: 38237.
Beyth S, Borovsky Z, Mevorach D, et al. Human mesenchymal stem cells alter antigen-presenting cell maturation and induce T-cell unresponsiveness. Blood 2005; 105: 2214–9.
Li C, Zhang W, Jiang X, Mao N. Human-placenta-derived mesenchymal stem cells inhibit proliferation and function of allogeneic immune cells. Cell Tissue Res 2007; 330: 437–46.
Guttman-Yassky E, Krueger JG. Atopic dermatitis and psoriasis: two different immune diseases or one spectrum? Curr Opin Immunol 2017; 48: 68–73.
Woo YR, Cho DH, Park HJ. Molecular mechanisms and management of a cutaneous inflammatory disorder: psoriasis. Int J Mol Sci 2017: 18.
Patel DD, Kuchroo VK. Th17 cell pathway in human immunity: lessons from genetics and therapeutic interventions. Immunity 2015; 43: 1040–51.
Kagami S, Rizzo HL, Lee JJ, Koguchi Y, Blauvelt A. Circulating Th17, Th22, and Th1 cells are increased in psoriasis. J Invest Dermatol 2010; 130: 1373–83.
Harrington LE, Hatton RD, Mangan PR, et al. Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol 2005; 6: 1123–32.
Chen M, Peng J, Xie Q, et al. Mesenchymal stem cells alleviate moderate-to-severe psoriasis by reducing the production of type I interferon (IFN-I) by plasmacytoid dendritic cells (pDCs). Stem Cells Int 2019; 2019: 6961052.
Acknowledgements and disclosures
Acknowledgements: this work was supported by the National Natural Science Foundation of China (Grant no. 81773336, 81472888, 81401360). Conflicts of interest: none.
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Zhao, X., Jiao, J., Li, X. et al. Immunomodulatory effect of psoriasis-derived dermal mesenchymal stem cells on TH1/TH17 cells. Eur J Dermatol 31, 318–325 (2021). https://doi.org/10.1684/ejd.2021.4050
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DOI: https://doi.org/10.1684/ejd.2021.4050