title: CCL2 deficient mesenchymal stem cells fail to establish long-lasting contact with T cells and no longer ameliorate lupus symptoms.
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.Faslprmouse survival, decreased T cell infiltration in the kidneys, and reduced T cell cytokine expression. In vitro, allogeneic mouse MSCs inhibited MRL.FaslprT cell proliferation and cytokine production. Time-lapse imaging revealed that MSCs recruited MRL.FaslprT 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-γ production by T cells and upon transfer no longer prolonged survival of MRL.Faslprmice. 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.Faslprmice.
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 28160, Republic of Korea.
authors.forename: Hong Kyung
authors.initials: HK
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 28160, Republic of Korea.|Corestem Inc, Gyeonggi 13486, Republic of Korea.
authors.forename: Hyung Sook
authors.initials: HS
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 28160, Republic of Korea.
authors.forename: Ji Sung
authors.initials: JS
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 28160, Republic of Korea.
authors.forename: Yong Guk
authors.initials: YG
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 28160, Republic of Korea.
authors.forename: Ki Hwan
authors.initials: KH
authors.lastname: Park
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 28160, Republic of Korea.
authors.forename: Jae Hee
authors.initials: JH
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 28160, Republic of Korea.
authors.forename: Ki Hun
authors.initials: KH
authors.lastname: Kim
authors.affiliation: Corestem Inc, Gyeonggi 13486, Republic of Korea.
authors.forename: In Young
authors.initials: IY
authors.lastname: Chang
authors.affiliation: Hanyang University Hospital for Rheumatic Diseases, Seoul 04763, Republic of Korea.
authors.forename: Sang-Cheol
authors.initials: SC
authors.lastname: Bae
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 28160, Republic of Korea.
authors.forename: Youngsoo
authors.initials: Y
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 28160, Republic of Korea.
authors.forename: Jin Tae
authors.initials: JT
authors.lastname: Hong
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: John H
authors.initials: JH
authors.lastname: Kehrl
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 28160, Republic of Korea.
authors.forename: Sang-Bae
authors.initials: SB
authors.lastname: Han
mesh_terms: D000818:Animals; D002450:Cell Communication; D002465:Cell Movement; D018932:Chemokine CCL2 / Q000172:deficiency*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000473:pathology*; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D012995:Solubility; D013601:T-Lymphocytes / Q000378:metabolism*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D018932:Chemokine CCL2; D019010:Vascular Cell Adhesion Molecule-1