Critical role of CCL22/CCR4 axis in the maintenance of immune homeostasis during apoptotic cell clearance by splenic CD8[alpha]+ CD103+ dendritic cells

• Published in: Immunology Vol. 148; no. 2; p. 174
• Main Authors: Hao, Shengyu, Han, Xiaolei, Wang, Dan, Yang, Yang, Li, Qiuting, Li, Xiangzhi, Qiu, Chun-Hong
• Format: Journal Article
• Language: English
• Published: Oxford Wiley Subscription Services, Inc 01-06-2016
• Subjects: Dendritic cells; Homeostasis; Rodents; Spleen
• ISSN: 0019-2805; 1365-2567
• DOI: 10.1111/imm.12596

Summary 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 CD8[alpha]+ 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 CD8[alpha]+ 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 CD8[alpha]+ CD103+ DCs dominantly produce much higher CCL22 than CD8[alpha]+ CD103- DCs. Moreover, the transient deletion of CD8[alpha]+ 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-[gamma] in the spleen with the absence of CD8[alpha]+ 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 CD8[alpha]+ CD103+ DCs.