Endometrial mesenchymal stem/stromal cell modulation of T cell proliferation

Xiaoqing Yang, Meivita Devianti, Yuan H. Yang, Yih Rue Ong, Ker Sin Tan, Shanti Gurung, Jean L Tan, Dandan Zhu, Rebecca Lim, Caroline Eve Gargett, James A Deane

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Perivascular mesenchymal stem/stromal cells can be isolated from the human endometrium using the surface marker SUSD2 and are being investigated for use in tissue repair. Mesenchymal stem/stromal cells from other tissues modulate T cell responses via mechanisms including interleukin-10, prostaglandin E2, TGF-β1 and regulatory T cells. Animal studies demonstrate that endometrial mesenchymal stem/stromal cells can also modify immune responses to implanted mesh, but the mechanism/s they employ have not been explored. We examined the immunomodulatory properties of human endometrial mesenchymal stem/stromal cells on lymphocyte proliferation using mouse splenocyte cultures. Endometrial mesenchymal stem/stromal cells inhibited mitogen-induced lymphocyte proliferation in vitro in a dose-dependent manner. Inhibition of lymphocyte proliferation was not affected by blocking the mouse interleukin-10 receptor or inhibiting prostaglandin production. Endometrial mesenchymal stem/stromal cells continued to restrain lymphocyte proliferation in the presence of an inhibitor of TGF-β receptors, despite a reduction in regulatory T cells. Thus, the in vitro inhibition of mitogen-induced lymphocyte proliferation by endometrial mesenchymal stem/stromal cells occurs by a mechanism distinct from the interleukin-10, prostaglandin E2, TGF-β1 and regulatory T cell-mediated mechanisms employed by MSC from other tissues. eMSCs were shown to produce interleukin-17A and Dickkopf-1 which may contribute to their immunomodulatory properties. In contrast to MSC from other sources, systemic administration of endometrial mesenchymal stem/stromal cells did not inhibit swelling in a T cell-mediated model of skin inflammation. We conclude that, while endometrial mesenchymal stem/stromal cells can modify immune responses, their immunomodulatory repertoire may not be sufficient to restrain some T cell-mediated inflammatory events.
Original languageEnglish
Pages (from-to)43–52
Number of pages10
JournalReproduction
Volume57
Issue number1
DOIs
Publication statusPublished - Jan 2019

Cite this

Yang, X., Devianti, M., Yang, Y. H., Ong, Y. R., Tan, K. S., Gurung, S., ... Deane, J. A. (2019). Endometrial mesenchymal stem/stromal cell modulation of T cell proliferation. Reproduction, 57(1), 43–52. https://doi.org/10.1530/REP-18-0266
Yang, Xiaoqing ; Devianti, Meivita ; Yang, Yuan H. ; Ong, Yih Rue ; Tan, Ker Sin ; Gurung, Shanti ; Tan, Jean L ; Zhu, Dandan ; Lim, Rebecca ; Gargett, Caroline Eve ; Deane, James A. / Endometrial mesenchymal stem/stromal cell modulation of T cell proliferation. In: Reproduction. 2019 ; Vol. 57, No. 1. pp. 43–52.
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abstract = "Perivascular mesenchymal stem/stromal cells can be isolated from the human endometrium using the surface marker SUSD2 and are being investigated for use in tissue repair. Mesenchymal stem/stromal cells from other tissues modulate T cell responses via mechanisms including interleukin-10, prostaglandin E2, TGF-β1 and regulatory T cells. Animal studies demonstrate that endometrial mesenchymal stem/stromal cells can also modify immune responses to implanted mesh, but the mechanism/s they employ have not been explored. We examined the immunomodulatory properties of human endometrial mesenchymal stem/stromal cells on lymphocyte proliferation using mouse splenocyte cultures. Endometrial mesenchymal stem/stromal cells inhibited mitogen-induced lymphocyte proliferation in vitro in a dose-dependent manner. Inhibition of lymphocyte proliferation was not affected by blocking the mouse interleukin-10 receptor or inhibiting prostaglandin production. Endometrial mesenchymal stem/stromal cells continued to restrain lymphocyte proliferation in the presence of an inhibitor of TGF-β receptors, despite a reduction in regulatory T cells. Thus, the in vitro inhibition of mitogen-induced lymphocyte proliferation by endometrial mesenchymal stem/stromal cells occurs by a mechanism distinct from the interleukin-10, prostaglandin E2, TGF-β1 and regulatory T cell-mediated mechanisms employed by MSC from other tissues. eMSCs were shown to produce interleukin-17A and Dickkopf-1 which may contribute to their immunomodulatory properties. In contrast to MSC from other sources, systemic administration of endometrial mesenchymal stem/stromal cells did not inhibit swelling in a T cell-mediated model of skin inflammation. We conclude that, while endometrial mesenchymal stem/stromal cells can modify immune responses, their immunomodulatory repertoire may not be sufficient to restrain some T cell-mediated inflammatory events.",
author = "Xiaoqing Yang and Meivita Devianti and Yang, {Yuan H.} and Ong, {Yih Rue} and Tan, {Ker Sin} and Shanti Gurung and Tan, {Jean L} and Dandan Zhu and Rebecca Lim and Gargett, {Caroline Eve} and Deane, {James A}",
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Endometrial mesenchymal stem/stromal cell modulation of T cell proliferation. / Yang, Xiaoqing; Devianti, Meivita ; Yang, Yuan H.; Ong, Yih Rue; Tan, Ker Sin; Gurung, Shanti; Tan, Jean L; Zhu, Dandan; Lim, Rebecca; Gargett, Caroline Eve; Deane, James A.

In: Reproduction, Vol. 57, No. 1, 01.2019, p. 43–52.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Yang, Xiaoqing

AU - Devianti, Meivita

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AU - Ong, Yih Rue

AU - Tan, Ker Sin

AU - Gurung, Shanti

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AU - Deane, James A

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AB - Perivascular mesenchymal stem/stromal cells can be isolated from the human endometrium using the surface marker SUSD2 and are being investigated for use in tissue repair. Mesenchymal stem/stromal cells from other tissues modulate T cell responses via mechanisms including interleukin-10, prostaglandin E2, TGF-β1 and regulatory T cells. Animal studies demonstrate that endometrial mesenchymal stem/stromal cells can also modify immune responses to implanted mesh, but the mechanism/s they employ have not been explored. We examined the immunomodulatory properties of human endometrial mesenchymal stem/stromal cells on lymphocyte proliferation using mouse splenocyte cultures. Endometrial mesenchymal stem/stromal cells inhibited mitogen-induced lymphocyte proliferation in vitro in a dose-dependent manner. Inhibition of lymphocyte proliferation was not affected by blocking the mouse interleukin-10 receptor or inhibiting prostaglandin production. Endometrial mesenchymal stem/stromal cells continued to restrain lymphocyte proliferation in the presence of an inhibitor of TGF-β receptors, despite a reduction in regulatory T cells. Thus, the in vitro inhibition of mitogen-induced lymphocyte proliferation by endometrial mesenchymal stem/stromal cells occurs by a mechanism distinct from the interleukin-10, prostaglandin E2, TGF-β1 and regulatory T cell-mediated mechanisms employed by MSC from other tissues. eMSCs were shown to produce interleukin-17A and Dickkopf-1 which may contribute to their immunomodulatory properties. In contrast to MSC from other sources, systemic administration of endometrial mesenchymal stem/stromal cells did not inhibit swelling in a T cell-mediated model of skin inflammation. We conclude that, while endometrial mesenchymal stem/stromal cells can modify immune responses, their immunomodulatory repertoire may not be sufficient to restrain some T cell-mediated inflammatory events.

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SN - 1470-1626

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Yang X, Devianti M, Yang YH, Ong YR, Tan KS, Gurung S et al. Endometrial mesenchymal stem/stromal cell modulation of T cell proliferation. Reproduction. 2019 Jan;57(1):43–52. https://doi.org/10.1530/REP-18-0266