Myeloid-Derived Suppressor Cells Play Crucial Roles in the Regulation of Mouse Collagen-Induced Arthritis

被引：174

作者：

Fujii, Wataru ^{[1
]}

Ashihara, Eishi ^{[2
]}

Hirai, Hideyo ^{[3
]}

Nagahara, Hidetake ^{[1
]}

Kajitani, Naoko ^{[1
]}

Fujioka, Kazuki ^{[1
]}

Murakami, Ken ^{[1
]}

Seno, Takahiro ^{[1
,4
]}

Yamamoto, Aihiro ^{[1
]}

Ishino, Hidetaka ^{[1
]}

Kohno, Masataka ^{[1
]}

Maekawa, Taira ^{[3
]}

Kawahito, Yutaka ^{[1
]}

机构：

[1] Kyoto Prefectural Univ Med, Grad Sch Med Sci, Kyoto 6028566, Japan

[2] Kyoto Pharmaceut Univ, Dept Clin & Translat Physiol, Kyoto 6078414, Japan

[3] Kyoto Univ Hosp, Dept Transfus Med & Cell Therapy, Kyoto 6068507, Japan

[4] Kyoto Prefectural Univ Med, Dept Rheumat Dis & Joint Funct, Kyoto 6028566, Japan

来源：

JOURNAL OF IMMUNOLOGY | 2013年 / 191卷 / 03期

关键词：

COLONY-STIMULATING FACTOR; NECROSIS-FACTOR-ALPHA; RHEUMATOID-ARTHRITIS; TH17; CELLS; T-CELLS; CANCER; MICE; DISEASE; DIFFERENTIATION; INFLAMMATION;

D O I：

10.4049/jimmunol.1203535

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

Myeloid-derived suppressor cells (MDSCs) are of myeloid origin and are able to suppress T cell responses. The role of MDSCs in autoimmune diseases remains controversial, and little is known about the function of MDSCs in autoimmune arthritis. In this study, we clarify that MDSCs play crucial roles in the regulation of proinflammatory immune response in a collagen-induced arthritis (CIA) mouse model. MDSCs accumulated in the spleens of mice with CIA when arthritis severity peaked. These MDSCs inhibited the proliferation of CD4(+) T cells and their differentiation into Th17 cells in vitro. Moreover, MDSCs inhibited the production of IFN-gamma, IL-2, TNF-alpha, and IL-6 by CD4(+) T cells in vitro, whereas they promoted the production of IL-10. Adoptive transfer of MDSCs reduced the severity of CIA in vivo, which was accompanied by a decrease in the number of CD4(+) T cells and Th17 cells in the draining lymph nodes. However, depletion of MDSCs abrogated the spontaneous improvement of CIA. In conclusion, MDSCs in CIA suppress the progression of CIA by inhibiting the proinflammatory immune response of CD4(+) T cells. These observations suggest that MDSCs play crucial roles in the regulation of autoimmune arthritis, which could be exploited in new cell-based therapies for human rheumatoid arthritis.

引用

页码：1073 / 1081

页数：9

共 53 条

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