Tsukada Jun, Ozaki Akemi, Hanada Toshikatsu, Chinen Takatoshi, Abe Ryo, Yoshimura Akihiko, Kubo Masato
Laboratory for Signal Network, Research Center for Allergy and Immunology (RCAI), RIKEN Yokohama Institute, Suehiro-cho 1-7-22, Tsurumi, Yokohama, Kanagawa 230-0045, Japan.
Int Immunol. 2005 Sep;17(9):1167-78. doi: 10.1093/intimm/dxh294. Epub 2005 Aug 9.
The suppressor of cytokine signaling (SOCS) 1 is a negative regulator in multiple cytokine-related aspects to maintain immunological homeostasis. Here, we studied a role of SOCS1 on dendritic cell (DC) maturation in the mice lacking either TCRalpha chain or CD28 in SOCS1-deficient background, and found that the SOCS1 could restore acute phase of inflammatory response in SOCS1-deficient mice. The CD11c+ CD8- DC population in freshly isolated splenic DCs from normal mice highly expressed SOCS1. However, in SOCS1-deficient environment, the proportion of CD8alpha+ DCs (CD8 DCs) noticeably increased without affecting the cell number of conventional and plasmacytoid DC populations. This population revealed the CD11cdull CD8alpha+ CD11b- CD45RA- B220- phenotype, which is a minor population in normal mice. Localization of the abnormal CD8 DCs in splenic microenvironments was mainly restricted to deep within red pulp. The CD8 DCs secrete a large amount of IFN-gamma, IL-12 and B lymphocyte stimulator/B cell activation factor of the tumor necrosis factor family in response to LPS and CpG stimulation. This is responsible for the development of DC-mediated systemic autoimmunity in the old age of SOCS1-deficient mice. Moreover, the CD8 DC subsets expressed more indoleamine 2,3-dioxygenase and IL-10, and hence inhibit the allogeneic proliferative T cell response and antigen-induced Th1 responses. Therefore, SOCS1 expression during DC maturation plays a role in surveillance in controlling the aberrant expansion of abnormal DC subset to maintain homeostasis of immune system.
细胞因子信号转导抑制因子（SOCS）1是多种细胞因子相关方面的负调节因子，以维持免疫稳态。在此，我们研究了SOCS1在SOCS1缺陷背景下缺乏TCRα链或CD28的小鼠中对树突状细胞（DC）成熟的作用，发现SOCS1可以恢复SOCS1缺陷小鼠炎症反应的急性期。正常小鼠新鲜分离的脾脏DC中CD11c + CD8 - DC群体高表达SOCS1。然而，在SOCS1缺陷环境中，CD8α + DCs（CD8 DCs）的比例显著增加，而不影响常规和浆细胞样DC群体的细胞数量。该群体表现出CD11c低表达CD8α + CD11b - CD45RA - B220 - 表型，这是正常小鼠中的一个小群体。异常CD8 DCs在脾脏微环境中的定位主要局限于红髓深处。CD8 DCs在受到LPS和CpG刺激时分泌大量IFN - γ、IL - 12和肿瘤坏死因子家族的B淋巴细胞刺激因子/B细胞活化因子。这导致了SOCS1缺陷小鼠老年时DC介导的全身性自身免疫的发展。此外，CD8 DC亚群表达更多的吲哚胺2,3 - 双加氧酶和IL - 10，因此抑制同种异体增殖性T细胞反应和抗原诱导的Th1反应。因此，DC成熟过程中SOCS1的表达在监测中发挥作用，以控制异常DC亚群的异常扩增，从而维持免疫系统的稳态。
