Journal article
Protein Tyrosine Phosphatase SHP-1 Modulates T Cell Responses by Controlling Cbl-b Degradation
The Journal of immunology (1950), Vol.195(9), pp.4218-4227
11/01/2015
DOI: 10.4049/jimmunol.1501200
PMCID: PMC4610872
PMID: 26416283
Abstract
Previously, we demonstrated that CD28 and CTLA-4 signaling control Casitas-B-lineage lymphoma (Cbl)-b protein expression, which is critical for T cell activation and tolerance induction. However, the molecular mechanism(s) of this regulation remains to be elucidated. In this study, we found that Cbl-b fails to undergo tyrosine phosphorylation upon CD3 stimulation because SHP-1 is recruited to and dephosphorylates Cbl-b, whereas CD28 costimulation abrogates this interaction. In support of this finding, T cells lacking SHP-1 display heightened tyrosine phosphorylation and ubiquitination of Cbl-b upon TCR stimulation, which correlates with decreased levels of Cbl-b protein. The aberrant Th2 phenotype observed in T cell-specific Shp1(-/-) mice is reminiscent of heightened Th2 response in Cblb(-/-) mice. Indeed, overexpressing Cbl-b in T cell-specific Shp1(-/-) T cells not only inhibits heightened Th2 differentiation in vitro, but also Th2 responses and allergic airway inflammation in vivo. Therefore, SHP-1 regulates Cbl-b-mediated T cell responses by controlling its tyrosine phosphorylation and ubiquitination.
Details
- Title: Subtitle
- Protein Tyrosine Phosphatase SHP-1 Modulates T Cell Responses by Controlling Cbl-b Degradation
- Creators
- Yun Xiao - Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH 43210; Department of Nephrology, Xiangya Hospital, Central South University, Changsha, 410008 Hunan, People's Republic of China; Department of Nephrology, The First Affiliated Hospital, Guangzhou Medical University, 510120 Guangzhou, People's Republic of ChinaGuilin Qiao - Section of Nephrology, Department of Medicine, The University of Chicago, Chicago, IL 60637; andJuan Tang - Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH 43210; Department of Nephrology, Xiangya Hospital, Central South University, Changsha, 410008 Hunan, People's Republic of ChinaRong Tang - Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH 43210; Department of Nephrology, Xiangya Hospital, Central South University, Changsha, 410008 Hunan, People's Republic of ChinaHui Guo - Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH 43210Samantha Warwar - Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH 43210Wallace Y Langdon - School of Pathology and Laboratory Medicine, University of Western Australia, Perth, Western Australia 6009, AustraliaLijian Tao - Department of Nephrology, Xiangya Hospital, Central South University, Changsha, 410008 Hunan, People's Republic of China; jian.zhang@osumc.edu taolj@csu.edu.cnJian Zhang - Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH 43210; Section of Nephrology, Department of Medicine, The University of Chicago, Chicago, IL 60637; and jian.zhang@osumc.edu taolj@csu.edu.cn
- Resource Type
- Journal article
- Publication Details
- The Journal of immunology (1950), Vol.195(9), pp.4218-4227
- DOI
- 10.4049/jimmunol.1501200
- PMID
- 26416283
- PMCID
- PMC4610872
- NLM abbreviation
- J Immunol
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Publisher
- United States
- Grant note
- R01 AI090901 / NIAID NIH HHS R21 AI117547 / NIAID NIH HHS R21AI117547 / NIAID NIH HHS
- Language
- English
- Date published
- 11/01/2015
- Academic Unit
- Pathology
- Record Identifier
- 9984047687802771
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