Galectin-1 is a local but not systemic immunomodulatory factor in mesenchymal stromal cells

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• 作者：Roberta Fajka-Boja¹ ; Veronika S. Urbá ; n² ; ³ ; Gá ; bor J. Szebeni¹ ; Á ; gnes Czibula¹ ; Andrea Blaskó ; ¹ ; É ; va Kriston-Pá ; l¹ ; Ildikó ; Makra¹ ; ⁵ ; Á ; kos Hornung¹ ; ⁶ ; Enikő Szabó ; ¹ ; Ferenc Uher³ ; Ná ; ndor G. Than⁴ ; É ; va Monostori¹ ; ^{monostori.eva@brc.mta.hu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：apoptosis ; delayed type hypersensitivity ; galectin-1 ; immunosuppression ; mesenchymal stromal cells ; type I diabetes
• 刊名：Cytotherapy
• 出版年：2016
• 出版时间：March 2016
• 年：2016
• 卷：18
• 期：3
• 页码：360-370
• 全文大小：1465 K

文摘

Mesenchymal stromal cells (MSCs) have powerful immunosuppressive activity. This function of MSCs is attributed to plethora of the expressed immunosuppressive factors, such as galectin-1 (Gal-1), a pleiotropic lectin with robust anti-inflammatory effect. Nevertheless, whether Gal-1 renders or contributes to the immunosuppressive effect of MSCs has not been clearly established. Therefore, this question was the focus of a complex study.

Methods

MSCs were isolated from bone marrows of wild-type and Gal-1 knockout mice and their in vitro anti-proliferative and apoptosis-inducing effects on activated T cells were examined. The in vivo immunosuppressive activity was tested in murine models of type I diabetes and delayed-type hypersensitivity.

Results

Both Gal-1-expressing and -deficient MSCs inhibited T-cell proliferation. Inhibition of T-cell proliferation by MSCs was mediated by nitric oxide but not PD-L1 or Gal-1. In contrast, MSC-derived Gal-1 triggered apoptosis in activated T cells that were directly coupled to MSCs, representing a low proportion of the T-cell population. Furthermore, absence of Gal-1 in MSCs did not affect their in vivo immunosuppressive effect.

Conclusions

These results serve as evidence that Gal-1 does not play a role in the systemic immunosuppressive effect of MSCs. However, a local contribution of Gal-1 to modulation of T-cell response by direct cell-to-cell interaction cannot be excluded. Notably, this study serves a good model to understand how the specificity of a pleiotropic protein depends on the type and localization of the producing effector cell and its target.