Human Umbilical Cord Mesenchymal Stem Cells Inhibit T Follicular Helper Cell Expansion Through the Activation of iNOS in Lupus-Prone B6.MRL-Faslpr Mice.

In this study, we demonstrated that the frequency of Tfh cells was increased in lupus-prone B6.MRL-<em>Fas<sup>lpr</sup></em> (B6.<em>lpr</em>) mice and positively correlated to plasma cell proportions and serum total IgG as well as anti-dsDNA antibody levels. Transplantation of human umbilical cord mesenchymal stem cells (UC-MSCs) ameliorated lupus symptoms in B6.<em>lpr</em> mice, along with decreased percentages of Tfh cells. <em>In vitro</em> studies showed that the differentiation and proliferation of Tfh cells were markedly suppressed by UC-MSCs. The production of inducible nitric oxide synthase (iNOS) was dramatically upregulated in UC-MSCs when co-cultured with CD4<sup>+</sup> T cells directly, while adding the specific inhibitor of iNOS into co-culture system significantly reversed the inhibitory effect of UC-MSCs on Tfh cell generation. Interestingly, the efficacy of UC-MSCs in inhibiting Tfh cells was impaired in the transwell system, with the reduction of iNOS in both mRNA and protein levels. Taken together, our findings suggest that UC-MSCs could effectively inhibit Tfh cell expansion through the activation of iNOS in lupus-prone B6.<em>lpr</em> mice, which are highly dependent on cell-to-cell contacts. PMID: 28105982 [PubMed - as supplied by publisher]
Source: Cell Transplantation - Category: Cytology Authors: Tags: Cell Transplant Source Type: research