CCL2 deficient mesenchymal stem cells fail to establish long-lasting contact with T cells and no longer ameliorate lupus symptoms
- Title
- CCL2 deficient mesenchymal stem cells fail to establish long-lasting contact with T cells and no longer ameliorate lupus symptoms
- Author
- 배상철
- Keywords
- HEME OXYGENASE-1; DENDRITIC CELLS; STROMAL CELLS; LYMPH-NODES; ACTIVATION; TRANSPLANTATION; MRL/LPR; ERYTHEMATOSUS; PROLIFERATION; SUPPRESSION
- Issue Date
- 2017-01
- Publisher
- NATURE PUBLISHING GROUP
- Citation
- SCIENTIFIC REPORTS, v. 7, Article no. 41258
- Abstract
- Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disease characterized by autoantibody production. Mesenchymal stem cells (MSCs) ameliorate SLE symptoms by targeting T cells, whereas the mechanisms of their efficacy remain incompletely understood. In this study, we show that transfer of human MSCs increased MRL.Fas(lpr) mouse survival, decreased T cell infiltration in the kidneys, and reduced T cell cytokine expression. In vitro, allogeneic mouse MSCs inhibited MRL.Fas(lpr) T cell proliferation and cytokine production. Time-lapse imaging revealed that MSCs recruited MRL.Fas(lpr) T cells establishing long-lasting cellular contacts by enhancing T cell VCAM-1 expression in a CCL2-dependent manner. In contrast, CCL2 deficient MSCs did not induce T cell migration and VCAM-1 expression, resulting in insufficient cell-cell contact. Consequently, CCL2 deficient MSCs did not inhibit IFN-gamma production by T cells and upon transfer no longer prolonged survival of MRL.Fas(lpr) mice. Taken together, our imaging study demonstrates that CCL2 enables the prolonged MSC-T cell interactions needed for sufficient suppression of autoreactive T cells and helps to understand how MSCs ameliorate symptoms in lupus-prone MRL.Fas(lpr) mice.
- URI
- https://www.nature.com/articles/srep41258https://repository.hanyang.ac.kr/handle/20.500.11754/112367
- ISSN
- 2045-2322
- DOI
- 10.1038/srep41258
- Appears in Collections:
- COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
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