Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Interleukin-3 (IL-3) is a hematopoietic growth factor and critical regulator of inflammatory response such as sepsis. IL-3 binds to IL-3 receptor α (IL-3Rα), which is then associated with IL-3Rβ to initiate signaling. How IL-3-triggered physiological and pathological effects are regulated at the receptor level is unclear. Here, we show that the plasma membrane-associated E3 ubiquitin ligase MARCH3 negatively regulates IL-3-triggered signaling. MARCH3 is associated with IL-3Rα, mediates its K48-linked polyubiquitination at K377 and promotes its proteasomal degradation. MARCH3-deficiency promotes IL-3-triggered transcription of downstream effector genes and IL-3-induced expansion of myeloid cells. In the cecal ligation and puncture (CLP) model of sepsis, MARCH3-deficiency aggravates IL-3-ampified expression of inflammatory cytokines, organ damage and inflammatory death. Our findings suggest that regulation of IL-3Rα by MARCH3 plays an important role in IL-3-triggered physiological functions and inflammatory diseases.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8786845 | PMC |
| http://dx.doi.org/10.1038/s41392-021-00834-7 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The membrane-associated ubiquitin ligases MARCH2 and MARCH3 target TIM-1 to limit Zika virus infection.
Cell Mol Immunol
September 2025
Department of Infectious Diseases, Zhongnan Hospital of Wuhan University; Hubei Provincial Research Center for Basic Biological Sciences; Medical Research Institute; Frontier Science Center for Immunology and Metabolism; Taikang Center for Life and Medical Sciences; Wuhan University, Wuhan, 430071,
T-cell immunoglobulin mucin family member-1 (TIM-1, also known as HAVCR1/KIM-1) is a transmembrane glycoprotein that has been reported to act as an entry receptor for multiple flaviviruses including Zika virus (ZIKV). The post-translational regulation of TIM-1 and its effects on ZIKV infection are unclear. In this study, we identified the membrane-associated RING-CH-type finger (MARCH) E3 ubiquitin ligase family members MARCH2 and MARCH3 as critical negative regulators of TIM-1 under physiological conditions.
View Article and Find Full Text PDFThe membrane-associated ubiquitin ligases MARCH2 and MARCH3 target IL-5 receptor alpha to negatively regulate eosinophilic airway inflammation.
Cell Mol Immunol
October 2022
Department of Infectious Diseases, Zhongnan Hospital of Wuhan University; Medical Research Institute; Frontier Science Center for Immunology and Metabolism; Research Unit of Innate Immune and Inflammatory Diseases (2019RU063), Chinese Academy of Medical Sciences; Wuhan University, Wuhan, 430071, Chi
Interleukin 5 (IL-5) plays crucial roles in type 2-high asthma by mediating eosinophil maturation, activation, chemotaxis and survival. Inhibition of IL-5 signaling is considered a strategy for asthma treatment. Here, we identified MARCH2 and MARCH3 as critical negative regulators of IL-5-triggered signaling.
View Article and Find Full Text PDFLongitudinal trajectories of insomnia symptoms among college students during the COVID-19 lockdown in China.
J Psychosom Res
June 2022
School of Psychology, Centre for Studies of Psychological Applications, Guangdong Key Laboratory of Mental Health and Cognitive Science, Ministry of Education Key Laboratory of Brain Cognition and Educational Science, South China Normal University, Guangzhou, China. Electronic address:
Purpose: This study aimed to examine the patterns and predictors of the trajectories of college students' insomnia symptoms across different stages of the COVID-19 pandemic.
Methods: A total of 35,516 college students completed three online surveys during the COVID-19 outbreak period (3-10 February 2020), initial remission period (24 March-3 April 2020), and effective control period (1-15 June 2020), respectively. These surveys measured the participants' socio-demographic and pandemic related factors, insomnia symptoms, mental health status, and psychosocial factors.
MARCH3 negatively regulates IL-3-triggered inflammatory response by mediating K48-linked polyubiquitination and degradation of IL-3Rα.
Signal Transduct Target Ther
January 2022
Department of Infectious Diseases, Zhongnan Hospital of Wuhan University, Medical Research Institute, Frontier Science Center for Immunology and Metabolism, Research Unit of Innate Immune and Inflammatory Diseases, Chinese Academy of Medical Sciences, Wuhan University, 430071, Wuhan, China. shuli@wh
Interleukin-3 (IL-3) is a hematopoietic growth factor and critical regulator of inflammatory response such as sepsis. IL-3 binds to IL-3 receptor α (IL-3Rα), which is then associated with IL-3Rβ to initiate signaling. How IL-3-triggered physiological and pathological effects are regulated at the receptor level is unclear.
View Article and Find Full Text PDFThe membrane-associated E3 ubiquitin ligase MARCH3 downregulates the IL-6 receptor and suppresses colitis-associated carcinogenesis.
Cell Mol Immunol
December 2021
Department of Infectious Diseases, Zhongnan Hospital of Wuhan University; Medical Research Institute; Frontier Science Center for Immunology and Metabolism; Research Unit of Innate Immune and Inflammatory Diseases, Chinese Academy of Medical Sciences; Wuhan University, Wuhan, 430071, China. shuli@wh
The IL-6-STAT3 axis is critically involved in inflammation-associated carcinogenesis (IAC). How this axis is regulated to modulate IAC remains unknown. Here, we show that the plasma membrane-associated E3 ubiquitin ligase MARCH3 negatively regulates STAT3 activation triggered by IL-6, as well as another IL-6 subfamily member, Oncostatin M (OSM).
View Article and Find Full Text PDF