Role of endogenous inhibitors of cytokine signaling in allergic asthma.
T helper 2 cytokines, including interleukin (IL)-4, IL-5, and IL-13, play an important role in allergic immune disorders, such as bronchial asthma. These cytokines regulate diverse biological functions by binding to receptors at the cell surface to activate complex signal transduction pathways, including the Janus kinase-signal transducer and activator of transcription (JAK-STAT) and the Ras-extracellular signal-regulated kinase (ERK) signaling pathways. The suppressor of cytokine signaling (SOCS) family proteins has been shown to regulate the JAK-STAT pathway, and the Sprouty-related EVH1-domain-containing protein (SPRED) family proteins regulate the Ras-ERK pathway. SOCS3 and SOCS5 are predominantly expressed in Th2 and Th1 cells, respectively, and they reciprocally inhibit the Th1 and Th2 differentiation processes. SOCS3 also has a role in Th3 differentiation. SPRED-1 is expressed in hematopoietic cells, including eosinophils, and negatively controls the eosinophil numbers and functions by modulating IL-5 signaling. Here, we discuss the role of SOCS and SPRED proteins in allergic asthma and explore the potential of these proteins as targets for therapeutic strategies in allergic asthma.
Inoue
Hiromasa
H
Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. inoue@kokyu.med.kyushu-u.ac.jp
Fukuyama
Satoru
S
Matsumoto
Koichiro
K
Kubo
Masato
M
Yoshimura
Akihiko
A
D001249:Asthma / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000502:physiology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology*; D050826:Suppressor of Cytokine Signaling Proteins / Q000502:physiology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D016207:Cytokines; D047908:Intracellular Signaling Peptides and Proteins; D050826:Suppressor of Cytokine Signaling Proteins