CCL2 deficient mesenchymal stem cells fail to establish long-lasting contact with T cells and no longer ameliorate lupus symptomsopen access
- Authors
- Lee, Hong Kyung; Kim, Hyung Sook; Kim, Ji Sung; Kim, Yong Guk; Park, Ki Hwan; Lee, Jae Hee; Kim, Ki Hun; Chang, In Young; Bae, Sang-Cheol; Kim, Youngsoo; Hong, Jin Tae; Kehrl, John H.; Han, Sang-Bae
- Issue Date
- Jan-2017
- Publisher
- NATURE PUBLISHING GROUP
- Citation
- SCIENTIFIC REPORTS, v.7
- Indexed
- SCIE
SCOPUS
- Journal Title
- SCIENTIFIC REPORTS
- Volume
- 7
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/3620
- DOI
- 10.1038/srep41258
- ISSN
- 2045-2322
- 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.
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