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Intraperitoneal infusion of mesenchymal stem/stromal cells prevents experimental autoimmune uveitis in mice.

Oh JY, Kim TW, Jeong HJ, Lee HJ, Ryu JS, Wee WR, Heo JW, Kim MK - Mediators Inflamm. (2014)

Bottom Line: The hMSCs did not reduce the levels of IL-1β, IL-6, IL-12, and IL-23 which are the cytokines that drive Th1/Th17 differentiation.Also, hMSCs did not induce CD4(+)CD25(+)Foxp3(+) cells.Our results support suggestions that hMSCs may offer a therapy for autoimmune diseases mediated by Th1/Th17 responses.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Seoul National University Hospital, Seoul 110-744, Republic of Korea ; Laboratory of Ocular Regenerative Medicine and Immunology, Seoul Artificial Eye Center, Seoul National University Hospital Biomedical Research Institute, Seoul 110-744, Republic of Korea.

ABSTRACT
Autoimmune uveitis is one of the leading causes of blindness. We here investigated whether intraperitoneal administration of human mesenchymal stem/stromal cells (hMSCs) might prevent development of experimental autoimmune uveitis (EAU) in mice. Time course study showed that the number of IFN-γ- or IL-17-expressing CD4(+) T cells was increased in draining lymph nodes (DLNs) on the postimmunization day 7 and decreased thereafter. The retinal structure was severely disrupted on day 21. An intraperitoneal injection of hMSCs at the time of immunization protected the retina from damage and suppressed the levels of proinflammatory cytokines in the eye. Analysis of DLNs on day 7 showed that hMSCs decreased the number of Th1 and Th17 cells. The hMSCs did not reduce the levels of IL-1β, IL-6, IL-12, and IL-23 which are the cytokines that drive Th1/Th17 differentiation. Also, hMSCs did not induce CD4(+)CD25(+)Foxp3(+) cells. However, hMSCs increased the level of an immunoregulatory cytokine IL-10 and the population of IL-10-expressing B220(+)CD19(+) cells. Together, data demonstrate that hMSCs attenuate EAU by suppressing Th1/Th17 cells and induce IL-10-expressing B220(+)CD19(+) cells. Our results support suggestions that hMSCs may offer a therapy for autoimmune diseases mediated by Th1/Th17 responses.

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Related in: MedlinePlus

Assay for inflammation- and immune-related cytokines in LNs. Real-time RT-PCR analysis showed that the levels of IL-17A and IFN-γ transcripts were increased in popliteal LNs on day 7 after EAU induction and significantly reduced by hMSCs (a). However, the levels of IL-10, TGF-β, and IL-6 were significantly increased by hMSCs (b, c). The levels of IL-1β, IL-12A, or IL-23 were not different between BSS- and hMSC-treated EAU mice (c, d). Data are presented in mean + SEM. n = 5 in each group.
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fig3: Assay for inflammation- and immune-related cytokines in LNs. Real-time RT-PCR analysis showed that the levels of IL-17A and IFN-γ transcripts were increased in popliteal LNs on day 7 after EAU induction and significantly reduced by hMSCs (a). However, the levels of IL-10, TGF-β, and IL-6 were significantly increased by hMSCs (b, c). The levels of IL-1β, IL-12A, or IL-23 were not different between BSS- and hMSC-treated EAU mice (c, d). Data are presented in mean + SEM. n = 5 in each group.

Mentions: We next investigated whether the tissue-protective effects of hMSCs might be due to the influence of hMSCs on the development of Th1, Th17, or γδ T cells that are pathogenic effectors in uveitis [3, 4]. Time course study showed that the percentage of IFN-γ-expressing CD4+ cells, IL-17A-expressing CD4+ cells, and γδ TCR-expressing CD4+ cells was significantly increased in popliteal and inguinal LNs of EAU mice on day 7 and decreased thereafter to baseline levels (Figure 2, Supplemental Figure 1 (see Supplemental Figure 1 available online at http://dx.doi.org/10.1155/2014/624640)). Treatment with hMSCs significantly reduced the percentage of Th1 and Th17 cells in popliteal and inguinal LNs on day 7 (Figure 2). Consistently, the levels of IL-17A and IFN-γ transcripts were significantly reduced by hMSCs, compared to the BSS-treated controls (Figure 3(a)). However, the percentage of γδ T cells was not affected by hMSC treatment (Supplemental Figure 1).


Intraperitoneal infusion of mesenchymal stem/stromal cells prevents experimental autoimmune uveitis in mice.

Oh JY, Kim TW, Jeong HJ, Lee HJ, Ryu JS, Wee WR, Heo JW, Kim MK - Mediators Inflamm. (2014)

Assay for inflammation- and immune-related cytokines in LNs. Real-time RT-PCR analysis showed that the levels of IL-17A and IFN-γ transcripts were increased in popliteal LNs on day 7 after EAU induction and significantly reduced by hMSCs (a). However, the levels of IL-10, TGF-β, and IL-6 were significantly increased by hMSCs (b, c). The levels of IL-1β, IL-12A, or IL-23 were not different between BSS- and hMSC-treated EAU mice (c, d). Data are presented in mean + SEM. n = 5 in each group.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4127236&req=5

fig3: Assay for inflammation- and immune-related cytokines in LNs. Real-time RT-PCR analysis showed that the levels of IL-17A and IFN-γ transcripts were increased in popliteal LNs on day 7 after EAU induction and significantly reduced by hMSCs (a). However, the levels of IL-10, TGF-β, and IL-6 were significantly increased by hMSCs (b, c). The levels of IL-1β, IL-12A, or IL-23 were not different between BSS- and hMSC-treated EAU mice (c, d). Data are presented in mean + SEM. n = 5 in each group.
Mentions: We next investigated whether the tissue-protective effects of hMSCs might be due to the influence of hMSCs on the development of Th1, Th17, or γδ T cells that are pathogenic effectors in uveitis [3, 4]. Time course study showed that the percentage of IFN-γ-expressing CD4+ cells, IL-17A-expressing CD4+ cells, and γδ TCR-expressing CD4+ cells was significantly increased in popliteal and inguinal LNs of EAU mice on day 7 and decreased thereafter to baseline levels (Figure 2, Supplemental Figure 1 (see Supplemental Figure 1 available online at http://dx.doi.org/10.1155/2014/624640)). Treatment with hMSCs significantly reduced the percentage of Th1 and Th17 cells in popliteal and inguinal LNs on day 7 (Figure 2). Consistently, the levels of IL-17A and IFN-γ transcripts were significantly reduced by hMSCs, compared to the BSS-treated controls (Figure 3(a)). However, the percentage of γδ T cells was not affected by hMSC treatment (Supplemental Figure 1).

Bottom Line: The hMSCs did not reduce the levels of IL-1β, IL-6, IL-12, and IL-23 which are the cytokines that drive Th1/Th17 differentiation.Also, hMSCs did not induce CD4(+)CD25(+)Foxp3(+) cells.Our results support suggestions that hMSCs may offer a therapy for autoimmune diseases mediated by Th1/Th17 responses.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Seoul National University Hospital, Seoul 110-744, Republic of Korea ; Laboratory of Ocular Regenerative Medicine and Immunology, Seoul Artificial Eye Center, Seoul National University Hospital Biomedical Research Institute, Seoul 110-744, Republic of Korea.

ABSTRACT
Autoimmune uveitis is one of the leading causes of blindness. We here investigated whether intraperitoneal administration of human mesenchymal stem/stromal cells (hMSCs) might prevent development of experimental autoimmune uveitis (EAU) in mice. Time course study showed that the number of IFN-γ- or IL-17-expressing CD4(+) T cells was increased in draining lymph nodes (DLNs) on the postimmunization day 7 and decreased thereafter. The retinal structure was severely disrupted on day 21. An intraperitoneal injection of hMSCs at the time of immunization protected the retina from damage and suppressed the levels of proinflammatory cytokines in the eye. Analysis of DLNs on day 7 showed that hMSCs decreased the number of Th1 and Th17 cells. The hMSCs did not reduce the levels of IL-1β, IL-6, IL-12, and IL-23 which are the cytokines that drive Th1/Th17 differentiation. Also, hMSCs did not induce CD4(+)CD25(+)Foxp3(+) cells. However, hMSCs increased the level of an immunoregulatory cytokine IL-10 and the population of IL-10-expressing B220(+)CD19(+) cells. Together, data demonstrate that hMSCs attenuate EAU by suppressing Th1/Th17 cells and induce IL-10-expressing B220(+)CD19(+) cells. Our results support suggestions that hMSCs may offer a therapy for autoimmune diseases mediated by Th1/Th17 responses.

Show MeSH
Related in: MedlinePlus