The role of suppressor of cytokine signaling 1 as a negative regulator for aberrant expansion of CD8α+ dendritic cell subset

Jun Tsukada, Akemi Ozaki, Toshikatsu Hanada, Takatoshi Chinen, Ryo Abe, Akihiko Yoshimura, Masato Kubo

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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 TCRα 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 CD8α+ DCs (CD8 DCs) noticeably increased without affecting the cell number of conventional and plasmacytoid DC populations. This population revealed the CD11cdull CD8α+ 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-γ, 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.

Original languageEnglish
Pages (from-to)1167-1178
Number of pages12
JournalInternational Immunology
Volume17
Issue number9
DOIs
Publication statusPublished - 2005 Sep
Externally publishedYes

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Keywords

  • Antigen presentation
  • CD8
  • Dendritic cell
  • SOCS1

ASJC Scopus subject areas

  • Immunology

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