Socs, Spred, And Nr4a: Negative Regulators Of Cytokine Signaling And Transcription In Immune Tolerance

Akihiko Yoshimura, Daisuke Aki, Minako Ito

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)


Cytokines are important intercellular communication tools for immunity. Most cytokines utilize the JAK-STAT and Ras-ERK pathways to promote gene transcription and proliferation; however, this signaling is tightly regulated. The suppressor of cytokine signaling (SOCS) family and Spred family are a representative negative regulators of the JAK-STAT pathway and the Ras-ERK pathway, respectively. The SOCS family regulates the differentiation and function of CD4+T cells, CD8+T cells, and regulatory T cells, and is involved in immune tolerance, anergy, and exhaustion. Spred family proteins have been shown to inactivate Ras by recruiting the Ras-GTPase neurofibromatosis type 1 (NF1) protein. Human genetic analysis has shown that SOCS family members are strongly associated with autoimmune diseases, allergies, and tumorigenesis, and SPRED1 is involved in NF1-like syndromes and tumors. We also identified the NR4a family of nuclear receptors as a key transcription factor for immune tolerance that suppresses cytokine expression and induces various immuno-regulatory molecules including SOCS1.

Original languageEnglish
Pages (from-to)277-291
Number of pages15
JournalProceedings of the Japan Academy Series B: Physical and Biological Sciences
Issue number6
Publication statusPublished - 2021

All Science Journal Classification (ASJC) codes

  • Agricultural and Biological Sciences(all)
  • Physics and Astronomy(all)


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