title: Critical role of CCL22/CCR4 axis in the maintenance of immune homeostasis during apoptotic cell clearance by splenic CD8α(+) CD103(+) dendritic cells.
abstract: Macrophages and dendritic cells (DCs) in murine spleen are essential for the maintenance of immune homeostasis by elimination of blood-borne foreign particles and organisms. It has been reported that splenic DCs, especially CD8α(+) CD103(+) DCs, are responsible for tolerance to apoptosis-associated antigens. However, the molecular mechanism by which these DCs maintain immune homeostasis by blood-borne apoptotic cell clearance remains elusive. Here, we found that the CCL22/CCR4 axis played a critical role in the maintenance of immune homeostasis during apoptotic cell clearance by splenic CD8α(+) CD103(+) DCs. The present results revealed that systemic administration of apoptotic cells rapidly induced a large number of CCL22 and CCR4(+) regulatory T (Treg) cells in the spleen of C57BL/6J mice. Further study demonstrated that CD8α(+) CD103(+) DCs dominantly produce much higher CCL22 than CD8α(+) CD103(-) DCs. Moreover, the transient deletion of CD8α(+) CD103(+) DCs caused a decrease in CCL22 levels together with CCR4(+) Treg cell percentage. Subsequently, the levels of some pro-inflammatory cytokines, such as interleukin-17 and interferon-γ in the spleen with the absence of CD8α(+) CD103(+) DCs increased in response to the administration of apoptotic cells. Hence, intravenous injection of apoptotic cells induced a subsequent increase in CCL22 expression and CCR4(+) Treg cells, which contribute to the maintenance of immune homeostasis at least partially by splenic CD8α(+) CD103(+) DCs.
authors: Department of Cell Biology, Shandong University School of Medicine, Jinan, Shandong, China.
authors: Shengyu
authors: S
authors: Hao
authors: Department of Cell Biology, Shandong University School of Medicine, Jinan, Shandong, China.
authors: Xiaolei
authors: X
authors: Han
authors: Department of Cell Biology, Shandong University School of Medicine, Jinan, Shandong, China.
authors: Dan
authors: D
authors: Wang
authors: Department of Cell Biology, Shandong University School of Medicine, Jinan, Shandong, China.
authors: Yang
authors: Y
authors: Yang
authors: Department of Cell Biology, Shandong University School of Medicine, Jinan, Shandong, China.
authors: Qiuting
authors: Q
authors: Li
authors: Department of Cell Biology, Shandong University School of Medicine, Jinan, Shandong, China.
authors: Xiangzhi
authors: X
authors: Li
authors: Department of Cell Biology, Shandong University School of Medicine, Jinan, Shandong, China.
authors: Chun-Hong
authors: CH
authors: Qiu
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis / Q000276:immunology*; D016827:CD8 Antigens / Q000378:metabolism; D002478:Cells, Cultured; D054422:Chemokine CCL22 / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology*; D006706:Homeostasis / Q000276:immunology; D039001:Integrin alpha Chains / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D054398:Receptors, CCR4 / Q000378:metabolism*; D013154:Spleen / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D016827:CD8 Antigens; C431698:CD8alpha antigen; C515483:Ccl22 protein, mouse; C515355:Ccr4 protein, mouse; D054422:Chemokine CCL22; D039001:Integrin alpha Chains; D020381:Interleukin-17; D054398:Receptors, CCR4; C091367:alpha E integrins; D007371:Interferon-gamma
keywords: CCL22; CCR4+ regulatory T cells; CD8α+ CD103+ dendritic cells; spleen