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SOCS, SPRED, and NR4a: Negative regulators of cytokine signaling and transcription in immune tolerance

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 re...

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Detalles Bibliográficos
Autores principales: YOSHIMURA, Akihiko, AKI, Daisuke, ITO, Minako
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Japan Academy 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8403526/
https://www.ncbi.nlm.nih.gov/pubmed/34121041
http://dx.doi.org/10.2183/pjab.97.016
Descripción
Sumario: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.