title: Rapid Inflammation in Mice Lacking Both SOCS1 and SOCS3 in Hematopoietic Cells.
abstract: The Suppressors of Cytokine Signalling (SOCS) proteins are negative regulators of cytokine signalling required to prevent excess cellular responses. SOCS1 and SOCS3 are essential to prevent inflammatory disease, SOCS1 by attenuating responses to IFNγ and gamma-common (γc) cytokines, and SOCS3 via regulation of G-CSF and IL-6 signalling. SOCS1 and SOCS3 show significant sequence homology and are the only SOCS proteins to possess a KIR domain. The possibility of overlapping or redundant functions was investigated in inflammatory disease via generation of mice lacking both SOCS1 and SOCS3 in hematopoietic cells. Loss of SOCS3 significantly accelerated the pathology and inflammatory disease characteristic of SOCS1 deficiency. We propose a model in which SOCS1 and SOCS3 operate independently to control specific cytokine responses and together modulate the proliferation and activation of lymphoid and myeloid cells to prevent rapid inflammatory disease.
authors: Cancer and Haematology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.|Division of Transfusion and Regenerative Medicine, Niigata University Medical and Dental Hospital, Niigata, Japan.
authors: Takashi
authors: T
authors: Ushiki
authors: Molecular Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.|Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
authors: Nicholas D
authors: ND
authors: Huntington
authors: Cancer and Haematology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.|Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
authors: Stefan P
authors: SP
authors: Glaser
authors: Cancer and Haematology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
authors: Hiu
authors: H
authors: Kiu
authors: Cancer and Haematology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
authors: Angela
authors: A
authors: Georgiou
authors: Cancer and Haematology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.|Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
authors: Jian-Guo
authors: JG
authors: Zhang
authors: Cancer and Haematology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.|Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
authors: Donald
authors: D
authors: Metcalf
authors: Cancer and Haematology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.|Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
authors: Nicos A
authors: NA
authors: Nicola
authors: Cancer and Haematology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.|Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
authors: Andrew W
authors: AW
authors: Roberts
authors: Cancer and Haematology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.|Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
authors: Warren S
authors: WS
authors: Alexander
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D016179:Granulocyte Colony-Stimulating Factor / Q000096:biosynthesis; D007249:Inflammation / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000071222:Suppressor of Cytokine Signaling 1 Protein / Q000235:genetics / Q000378:metabolism*; D000071223:Suppressor of Cytokine Signaling 3 Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: C491590:Socs1 protein, mouse; C491411:Socs3 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D016179:Granulocyte Colony-Stimulating Factor