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Immunology

Mesenchymal stromal cells infusions improve refractory chronic graft versus host disease through an increase of CD5+ regulatory B cells producing interleukin 10

Leukemia volume 29, pages 636–646 (2015)Cite this article

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Abstract

Refractory chronic graft-versus-host disease (cGVHD) is a significant complication resulting from allogeneic hematopoietic stem cell transplantation (HSCT). Mesenchymal stromal cells (MSCs) have shown promise for treating refractory cGVHD, but the favorable effects of MSCs therapy in cGVHD are complex and not fully understood. In this prospective clinical study, 20 of 23 cGVHD patients had a complete response or partial response in a 12-month follow-up study. The most marked improvements in cGVHD symptoms were observed in the skin, oral mucosa and liver. Clinical improvement was accompanied by a significantly increased number of interleukin (IL)-10-producing CD5+ B cells. Importantly, CD5+ B cells from cGVHD patients showed increased IL-10 expression after MSCs treatment, which was associated with reduced inflammatory cytokine production by T cells. Mechanistically, MSCs could promote the survival and proliferation of CD5+ regulatory B cells (Bregs), and indoleamine 2, 3-dioxygenase partially participates in the MSC-mediated effects on Breg cells. Thus, CD5+ Breg cells may have an important role in the process of MSC-induced amelioration of refractory cGVHD and may provide new clues to reveal novel mechanisms of action for MSCs.

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Acknowledgements

We thank Drs Armand Keating, Chee Peng Sum and Xianchang Li for their comments on this article. This study was supported by the National Basic Research Program of China (2012CBA01302 and 2010CB945401), the National Natural Science Foundation of China (81270646 and 31171398), the Key Scientific and Technological Projects of Guangdong Province (2007A032100003), the National Natural Science Foundation of Guangdong Province (S2013030013305), the Project of Guangdong Translational Medicine Public Platform and the Key Scientific and Technological Program of Guangzhou City (201400000003-3, 201300000089 and 2010U1-E00551), Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme (GDUPS, 2013). The funding agencies had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript.

Author Contributions

YP, QL and APX designed the study, analyzed and interpreted the data and wrote the paper; XC and XZ performed the western blot and small interfering RN analyses; MK and KH performed the cell isolations and the survival and proliferation analyses; LL, HL and MZ performed the cell isolations and the analysis of the patients’ phenotypes; QL performed the ELISPOT; XL performed the cell sorting; QZ provided helpful discussions and edited the paper; FH, ZF and JS collected the patient samples and information and assessed the patients’ statuses.

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Author notes

  1. Y Peng, X Chen and Q Liu: These authors contributed equally to this work.

Authors and Affiliations

  1. Center for Stem Cell Biology and Tissue Engineering, The Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, China

    Y Peng, X Chen, X Zhang, Q Liu, M Ke, X Li & A P Xiang

  2. Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China

    Q Liu, F Huang, Z Fan & J Sun

  3. Department of Pediatrics, Second Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China

    K Huang

  4. Organ Transplant Center, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China

    L Liu

  5. Guangdong Institute for Food and Drug Control, Guangdong Food and Drug Administration, Guangzhou, China

    H Li

  6. Department of Laboratory Medicine, Guangdong General Hospital, Guangzhou, China

    M Zhou

  7. Department of Oral and Maxillofacial Surgery and Pharmacology, School of the Dental Medicine, University of Pennsylvania, Pennsylvania, PA, USA

    Q Zhang

  8. Department of Biochemistry, Zhongshan Medical School, Sun Yat-Sen University, Guangzhou, China

    A P Xiang

  9. Cell-Gene Therapy Translational Medicine Research Center, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China

    A P Xiang

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Correspondence to A P Xiang.

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Peng, Y., Chen, X., Liu, Q. et al. Mesenchymal stromal cells infusions improve refractory chronic graft versus host disease through an increase of CD5+ regulatory B cells producing interleukin 10. Leukemia 29, 636–646 (2015). https://doi.org/10.1038/leu.2014.225

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