Abstract
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-1low cells had a suppressive effect on CD4+ T-cell proliferation, which was restored by an arginase-1 inhibitor. CD11b+ GR-1low cells increased in percentage during disease progression in kidney and blood. The number of migrated CD11b+ GR-1low cells increased in the presence of monocyte chemoattractant protein-1/CCL2.
Conclusion
We assessed the involvement of CD11b+ GR-1low 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.
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Acknowledgments
Y I is a recipient of a Grant-in-Aid from the Ministry of Education, Science, Sports, and Culture in Japan. T W is a recipient of a Grant-in-Aid from the Ministry of Education, Science, Sports, and Culture in Japan and Takeda Science Foundation.
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The authors have no confliction of interest.
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Iwata, Y., Furuichi, K., Kitagawa, K. et al. Involvement of CD11b+ GR-1low cells in autoimmune disorder in MRL-Fas lpr mouse. Clin Exp Nephrol 14, 411–417 (2010). https://doi.org/10.1007/s10157-010-0309-9
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DOI: https://doi.org/10.1007/s10157-010-0309-9