Involvement of CD11b+ GR-1 low cells in autoimmune disorder in MRL-Fas lpr mouse.
OBJECTIVE
Myeloid-derived suppressor cells (MDSCs) have been identified as immunosuppressive cells in tumor-related inflammation. However, the pathogenesis of MDSCs for autoimmune disease has not been investigated as yet. The aim of this study was to address whether MDSCs contribute to autoimmune organ injury in lupus-prone mice.


METHODS
MDSCs were analyzed by flow cytometric staining of CD11b(+) GR-1(+) in MRL-Fas ( lpr ) mice. CD4(+) T-cell proliferation assay was performed by coculture with CD11b(+) GR-1(+) splenocytes. The percentage of immunosuppressive cells was examined during disease progression. Expression of chemokine receptor on immunosuppressive cells was analyzed, and chemotaxis assay was performed.


RESULTS
CD11b(+) GR-1(low) cells had a suppressive effect on CD4(+) T-cell proliferation, which was restored by an arginase-1 inhibitor. CD11b(+) GR-1(low) cells increased in percentage during disease progression in kidney and blood. The number of migrated CD11b(+) GR-1(low) cells increased in the presence of monocyte chemoattractant protein-1/CCL2.


CONCLUSIONS
We assessed the involvement of CD11b(+) GR-1(low) cells in autoimmune disorder in MRL-Fas(lpr) mice. These cells regulate immunological responses via CCL2/CCR2 signaling. The regulation of immunosuppressive monocytes may provide novel therapeutic strategy for organ damage in autoimmune diseases.
Iwata
Yasunori
Y
Department of Disease Control and Homeostasis, Institute of Medical, Pharmaceutical and Health Sciences, Faculty of Medicine, Kanazawa University, Kanazawa, Japan.
Furuichi
Kengo
K
Kitagawa
Kiyoki
K
Hara
Akinori
A
Okumura
Toshiya
T
Kokubo
Satoshi
S
Shimizu
Kazuaki
K
Sakai
Norihiko
N
Sagara
Akihiro
A
Kurokawa
Yukie
Y
Ueha
Satoshi
S
Matsushima
Kouji
K
Kaneko
Shuichi
S
Wada
Takashi
T
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D039481:CD11b Antigen / Q000276:immunology*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000276:immunology; D018920:Coculture Techniques; D007668:Kidney / Q000166:cytology / Q000276:immunology / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D051379:Mice; D019463:Mice, Inbred MRL lpr; D022423:Myeloid Cells / Q000166:cytology / Q000276:immunology*; D054390:Receptors, CCR2 / Q000276:immunology; D019707:Receptors, Chemokine / Q000235:genetics / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology
D039481:CD11b Antigen; C491768:Ccl2 protein, mouse; C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; C503133:Gr-1 protein, mouse; D054390:Receptors, CCR2; D019707:Receptors, Chemokine