Related Experiment Video
Updated: Mar 15, 2026
Combining Intravital Fluorescent Microscopy IVFM with Genetic Models to Study Engraftment Dynamics of Hematopoietic Cells to Bone Marrow Niches
Published on: March 21, 2017
Rapid Inflammation in Mice Lacking Both SOCS1 and SOCS3 in Hematopoietic Cells
Takashi Ushiki1,2, Nicholas D Huntington3,4, Stefan P Glaser1,4
1Cancer and Haematology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
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.
Insights
Suppressors of Cytokine Signalling (SOCS) 1 and SOCS3 proteins are crucial for preventing inflammatory disease. Loss of SOCS3 accelerated SOCS1 deficiency, indicating their combined role in regulating immune cell responses.
Area of Science:
- Immunology
- Molecular Biology
Background:
- Suppressors of Cytokine Signalling (SOCS) proteins are negative regulators of cytokine signaling.
- SOCS1 and SOCS3 are vital for preventing inflammatory diseases by modulating specific cytokine responses.
- SOCS1 and SOCS3 share sequence homology and possess a KIR domain, suggesting potential overlapping functions.
Purpose of the Study:
- To investigate the overlapping or redundant functions of SOCS1 and SOCS3 in inflammatory disease.
- To determine the combined effect of SOCS1 and SOCS3 deficiency in hematopoietic cells on inflammatory pathology.
Main Methods:
- Generation of mice lacking both SOCS1 and SOCS3 in hematopoietic cells.
- Analysis of inflammatory disease pathology and immune cell responses in knockout mice.
Main Results:
- Loss of SOCS3 significantly accelerated the inflammatory disease characteristic of SOCS1 deficiency.
- Hematopoietic cells lacking both SOCS1 and SOCS3 exhibited exacerbated inflammatory responses.
- SOCS1 and SOCS3 were found to modulate the proliferation and activation of lymphoid and myeloid cells.
Conclusions:
- SOCS1 and SOCS3 operate independently to control specific cytokine responses.
- Together, SOCS1 and SOCS3 play a critical role in preventing rapid inflammatory disease by modulating immune cell activity.
Related Concept Videos
01:01Regulation of Hematopoietic Stem Cells
01:19Multipotency of Hematopoietic Stem Cells