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The ERM Protein Moesin Regulates CD8 + Regulatory T Cell Homeostasis and Self-Tolerance.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2017 Nov 15; Vol. 199 (10), pp. 3418-3426. Date of Electronic Publication: 2017 Oct 04. - Publication Year :
- 2017
-
Abstract
- The ezrin-radixin-moesin (ERM) proteins are a family of membrane-associated proteins that link membrane proteins with actin filaments in the cell cortex and regulate many cellular processes, including cell shape determination, membrane transport, and signal transduction. Lymphocytes predominantly express two ERM members, ezrin and moesin. Mutations in the moesin gene in humans are associated with primary immunodeficiency with profound lymphopenia, and moesin-deficient mice exhibit a similar lymphopenia phenotype. In this study, we show that aging moesin-deficient mice develop a systemic lupus erythematosus-like autoimmune phenotype, which is characterized by elevated serum autoantibody levels and glomerulonephritis. Younger moesin-deficient mice exhibited elevated basal levels of several Ig isotypes and enhanced Ab affinity maturation upon immunization. Germinal center B cells and follicular helper T cells spontaneously accumulated in unimmunized mice, and CD8 <superscript>+</superscript> CD44 <superscript>+</superscript> CD122 <superscript>+</superscript> Ly49 <superscript>+</superscript> regulatory T (CD8 <superscript>+</superscript> Tregs) cells, which inhibit the expansion of follicular helper T cells, were severely reduced in these mice. Isolated CD8 <superscript>+</superscript> Treg cells from moesin-deficient mice showed impaired proliferation in response to IL-15, which was accompanied by defects in STAT5 activation and IL-15Rα internalization, suggesting that moesin plays a key role in IL-15-mediated signaling. These findings underscore the importance of moesin in IL-15-dependent CD8 <superscript>+</superscript> Treg cell homeostasis and, thus, the control of self-tolerance.<br /> (Copyright © 2017 by The American Association of Immunologists, Inc.)
- Subjects :
- Animals
Autoantibodies blood
B-Lymphocytes immunology
CD8 Antigens metabolism
Cells, Cultured
Cytoskeletal Proteins metabolism
Disease Models, Animal
Glomerulonephritis
Homeostasis
Humans
Interleukin-15 metabolism
Lupus Erythematosus, Systemic genetics
Lymphopenia genetics
Membrane Proteins metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Microfilament Proteins genetics
STAT5 Transcription Factor metabolism
Self Tolerance
Lupus Erythematosus, Systemic immunology
Lymphopenia immunology
Microfilament Proteins metabolism
T-Lymphocytes, Helper-Inducer immunology
T-Lymphocytes, Regulatory immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 199
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 28978692
- Full Text :
- https://doi.org/10.4049/jimmunol.1700074