Skip to main content


Log in

Involvement of CD11b+ GR-1low cells in autoimmune disorder in MRL-Fas lpr mouse

  • Original Article
  • Published:
Clinical and Experimental Nephrology Aims and scope Submit manuscript



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.


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.


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.


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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others


  1. Serafini P, Borrello I, Bronte V. Myeloid suppressor cells in cancer: recruitment, phenotype, properties, and mechanisms of immune suppression. Semin Cancer Biol. 2006;16:53–65.

    Article  CAS  PubMed  Google Scholar 

  2. Talmadge JE, Donkor M, Scholar E. Inflammatory cell infiltration of tumors: Jekyll or Hyde. Cancer Metastasis Rev. 2007;26:373–400.

    Article  PubMed  Google Scholar 

  3. Marigo I, Dolcetti L, Serafini P, Zanovello P, Bronte V. Tumor-induced tolerance and immune suppression by myeloid derived suppressor cells. Immunol Rev. 2008;222:162–79.

    Article  CAS  PubMed  Google Scholar 

  4. Rodríguez PC, Ochoa AC. Arginine regulation by myeloid derived suppressor cells and tolerance in cancer: mechanisms and therapeutic perspectives. Immunol Rev. 2008;222:180–91.

    Article  PubMed  Google Scholar 

  5. Makarenkova VP, Bansal V, Matta BM, Perez LA, Ochoa JB. CD11b+/Gr-1+ myeloid suppressor cells cause T cell dysfunction after traumatic stress. J Immunol. 2006;176:2085–94.

    CAS  PubMed  Google Scholar 

  6. Marhaba R, Vitacolonna M, Hildebrand D, Baniyash M, Freyschmidt-Paul P, Zöller M. The importance of myeloid-derived suppressor cells in the regulation of autoimmune effector cells by a chronic contact eczema. J Immunol. 2007;179:5071–81.

    CAS  PubMed  Google Scholar 

  7. Zhu B, Bando Y, Xiao S, Yang K, Anderson AC, Kuchroo VK, et al. CD11b+Ly-6C(hi) suppressive monocytes in experimental autoimmune encephalomyelitis. J Immunol. 2007;179:5228–37.

    CAS  PubMed  Google Scholar 

  8. Haile LA, Wasielewski RV, Gamrekelashvili J, Krüger C, Bachmann O, Westendorf AM, et al. Myeloid-derived suppressor cells in inflammatory bowel disease: a new immunoregulatory pathway. Gastroenterology. 2008;135:871–81.

    Article  CAS  PubMed  Google Scholar 

  9. Filipazzi P, Valenti R, Huber V, Pilla L, Canese P, Iero M, et al. Identification of a new subset of myeloid suppressor cells in peripheral blood of melanoma patients with modulation by a granulocyte-macrophage colony-stimulation factor-based antitumor vaccine. J Clin Oncol. 2007;25:2546–53.

    Article  CAS  PubMed  Google Scholar 

  10. Huang B, Lei Z, Zhao J, Gong W, Liu J, Chen Z, et al. CCL2/CCR2 pathway mediates recruitment of myeloid suppressor cells to cancers. Cancer Lett. 2007;252:86–92.

    Article  CAS  PubMed  Google Scholar 

  11. Umemura N, Saio M, Suwa T, Kitoh Y, Bai J, Nonaka K, et al. Tumor-infiltrating myeloid-derived suppressor cells are pleiotropic-inflamed monocytes/macrophages that bear M1- and M2-type characteristics. J Leukoc Biol. 2008;83:1136–44.

    Article  CAS  PubMed  Google Scholar 

  12. Sawanobori Y, Ueha S, Kurachi M, Shimaoka T, Talmadge JE, Abe J, et al. Chemokine-mediated rapid turnover of myeloid-derived suppressor cells in tumor-bearing mice. Blood. 2008;111:5457–66.

    Article  CAS  PubMed  Google Scholar 

  13. Kelley VR, Wuthrich RP. Cytokines in the pathogenesis of systemic lupus erythematosus. Semin Nephrol. 1999;19:57–66.

    CAS  PubMed  Google Scholar 

  14. Pérez de Lema G, Maier H, Franz TJ, Escribese M, Chilla S, Segerer S, et al. Chemokine receptor Ccr2 deficiency reduces renal disease and prolongs survival in MRL/lpr lupus-prone mice. J Am Soc Nephrol. 2005;6:3592–601.

    Article  Google Scholar 

  15. Sakai N, Wada T, Yokoyama H, Lipp M, Ueha S, Matsushima K, et al. Secondary lymphoid tissue chemokine (SLC/CCL21)/CCR7 signaling regulates fibrocytes in renal fibrosis. Proc Natl Acad Sci USA. 2006;103:14098–103.

    Article  CAS  PubMed  Google Scholar 

  16. Iwata Y, Wada T, Furuichi K, Sakai N, Matsushima K, Yokoyama H, et al. p38 Mitogen-activated protein kinase contributes to autoimmune renal injury in MRL-Fas lpr mice. J Am Soc Nephrol. 2003;14:57–67.

    Article  CAS  PubMed  Google Scholar 

  17. Gallina G, Dolcetti L, Serafini P, De Santo C, Marigo I, Colombo MP, et al. Tumors induce a subset of inflammatory monocytes with immunosuppressive activity on CD8+ T cells. J Clin Invest. 2006;116:2777–90.

    Article  CAS  PubMed  Google Scholar 

  18. Xiao W, Hong H, Kawakami Y, Lowell CA, Kawakami T. Regulation of myeloproliferation and M2 macrophage programming in mice by Lyn/Hck, SHIP, and Stat5. J Clin Invest. 2008;118:924–34.

    CAS  PubMed  Google Scholar 

  19. Gordon S, Taylor PR. Monocyte and macrophage heterogeneity. Nat Rev Immunol. 2005;5:953–64.

    Article  CAS  PubMed  Google Scholar 

  20. Mantovani A, Sica A, Locati M. Macrophage polarization comes of age. Immunity. 2005;23:344–6.

    Article  CAS  PubMed  Google Scholar 

Download references


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.

Conflict of interest statement

The authors have no confliction of interest.

Author information

Authors and Affiliations


Corresponding author

Correspondence to Takashi Wada.

About this article

Cite this article

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).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: