Limits...
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.

Show MeSH

Related in: MedlinePlus

Assay for IL-10-expressing cells in LNs. Flow cytometric analysis of popliteal LNs on day 7 after EAU immunization showed that the percentages of IL-10+CD19+ (a) and IL-10+B220+CD19+ cells (b) were significantly increased in mice treated with hMSCs, compared to mice without EAU or BSS-treated EAU mice. Data are presented in mean ± SEM. n = 5 in each group.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4127236&req=5

fig4: Assay for IL-10-expressing cells in LNs. Flow cytometric analysis of popliteal LNs on day 7 after EAU immunization showed that the percentages of IL-10+CD19+ (a) and IL-10+B220+CD19+ cells (b) were significantly increased in mice treated with hMSCs, compared to mice without EAU or BSS-treated EAU mice. Data are presented in mean ± SEM. n = 5 in each group.

Mentions: To identify the IL-10-expressing cell population, we examined CD4+, CD19+, B220+, CD11b+, or CD11c+ cells in DLNs for IL-10 expression. We found that the percentage of IL-10+B220+CD19+ cells was markedly increased in popliteal LNs of hMSCs-treated EAU mice on day 7, compared to BSS-treated EAU mice (Figures 4(a) and 4(b)). However, IL-10 expression was not increased in CD4+, CD11b+, or CD11c+ cells (data not shown). Also, hMSCs did not increase the percentage of CD4+CD25+Foxp3+ Treg cells in popliteal or inguinal LNs at all examined time-points (Supplemental Figures 2(a) and 2(b)). Time course indicated that CD4+CD25+Foxp3+ cells initially increased in popliteal and inguinal LNs on day 7 after EAU induction and gradually decreased to baseline on days 14 and 21. On the contrary, CD4+CD25+Foxp3+ cells initially decreased in the spleen on day 7 and increased thereafter until day 21. The hMSCs significantly suppressed an increase of CD4+CD25+Foxp3+ cells in the spleen on days 14 and 21 (Supplemental Figure 2(c)), reflecting that hMSCs might suppress early inflammation that is required for initial Treg expansion [11].


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 IL-10-expressing cells in LNs. Flow cytometric analysis of popliteal LNs on day 7 after EAU immunization showed that the percentages of IL-10+CD19+ (a) and IL-10+B220+CD19+ cells (b) were significantly increased in mice treated with hMSCs, compared to mice without EAU or BSS-treated EAU mice. 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

fig4: Assay for IL-10-expressing cells in LNs. Flow cytometric analysis of popliteal LNs on day 7 after EAU immunization showed that the percentages of IL-10+CD19+ (a) and IL-10+B220+CD19+ cells (b) were significantly increased in mice treated with hMSCs, compared to mice without EAU or BSS-treated EAU mice. Data are presented in mean ± SEM. n = 5 in each group.
Mentions: To identify the IL-10-expressing cell population, we examined CD4+, CD19+, B220+, CD11b+, or CD11c+ cells in DLNs for IL-10 expression. We found that the percentage of IL-10+B220+CD19+ cells was markedly increased in popliteal LNs of hMSCs-treated EAU mice on day 7, compared to BSS-treated EAU mice (Figures 4(a) and 4(b)). However, IL-10 expression was not increased in CD4+, CD11b+, or CD11c+ cells (data not shown). Also, hMSCs did not increase the percentage of CD4+CD25+Foxp3+ Treg cells in popliteal or inguinal LNs at all examined time-points (Supplemental Figures 2(a) and 2(b)). Time course indicated that CD4+CD25+Foxp3+ cells initially increased in popliteal and inguinal LNs on day 7 after EAU induction and gradually decreased to baseline on days 14 and 21. On the contrary, CD4+CD25+Foxp3+ cells initially decreased in the spleen on day 7 and increased thereafter until day 21. The hMSCs significantly suppressed an increase of CD4+CD25+Foxp3+ cells in the spleen on days 14 and 21 (Supplemental Figure 2(c)), reflecting that hMSCs might suppress early inflammation that is required for initial Treg expansion [11].

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