Journal article
Membrane-organizing protein moesin controls Treg differentiation and antitumor immunity via TGF-beta signaling
The Journal of clinical investigation, Vol.127(4), pp.1321-1337
04/03/2017
DOI: 10.1172/JCI89281
PMCID: PMC5373867
PMID: 28287407
Abstract
Moesin is a member of the ezrin-radixin-moesin (ERM) family of proteins that are important for organizing membrane domains and receptor signaling and regulating the migration of effector T cells. Whether moesin plays any role during the generation of TGF-beta-induced Tregs (iTregs) is unknown. Here, we have discovered that moesin is translationally regulated by TGF-beta and is also required for optimal TGF-beta signaling that promotes efficient development of iTregs. Loss of moesin impaired the development and function of both peripherally derived iTregs and in vitro-induced Tregs. Mechanistically, we identified an interaction between moesin and TGF-beta receptor II (T beta RII) that allows moesin to control the surface abundance and stability of T beta RI and T beta RII. We also found that moesin is required for iTreg conversion in the tumor microenvironment, and the deletion of moesin from recipient mice supported the rapid expansion of adoptively transferred CD8(+) T cells against melanoma. Our study establishes moesin as an important regulator of the surface abundance and stability of T beta RII and identifies moesin's role in facilitating the efficient generation of iTregs. It also provides an advancement to our understanding about the role of the ERM proteins in regulating signal transduction pathways and suggests that modulation of moesin is a potential therapeutic target for Treg-related immune disorders.
Details
- Title: Subtitle
- Membrane-organizing protein moesin controls Treg differentiation and antitumor immunity via TGF-beta signaling
- Creators
- Ephraim A. Ansa-Addo - MUSC Hollings Cancer CenterYongliang Zhang - MUSC Hollings Cancer CenterYi Yang - MUSC Hollings Cancer CenterGeorge S. Hussey - Med Univ S Carolina, Hollings Canc Ctr, Dept Biochem & Mol Biol, Charleston, SC 29425 USABreege V. Howley - Med Univ S Carolina, Hollings Canc Ctr, Dept Biochem & Mol Biol, Charleston, SC 29425 USAMohammad Salem - MUSC Hollings Cancer CenterBrian Riesenberg - MUSC Hollings Cancer CenterShaoli Sun - Emory University HospitalDon C. Rockey - Medical University of South CarolinaSerhan Karvar - Medical University of South CarolinaPhilip H. Howe - Med Univ S Carolina, Hollings Canc Ctr, Dept Biochem & Mol Biol, Charleston, SC 29425 USABei Liu - MUSC Hollings Cancer CenterZihai Li - MUSC Hollings Cancer Center
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.127(4), pp.1321-1337
- Publisher
- Amer Soc Clinical Investigation Inc
- DOI
- 10.1172/JCI89281
- PMID
- 28287407
- PMCID
- PMC5373867
- ISSN
- 0021-9738
- eISSN
- 1558-8238
- Number of pages
- 17
- Grant note
- R01DK098819; U01AI12585; P01CA186866; R01CA188419; R01AI070603 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Flow Cytometry & Cell Sorting Unit U01AI125859 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) SmartState Endowed Chair Program of South Carolina R01DK098819 / NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) P30CA138313 / Cell & Molecular Imaging Shared Resource, Hollings Cancer Center, Medical University of South Carolina P01CA186866 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
- Language
- English
- Date published
- 04/03/2017
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984695682002771
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