Stat5a/b Are Essential for Normal Lymphoid Development and Differentiation

Cytokines that use the common gamma chain γc are critical for lymphoid development and function. Mutations of the IL-7 receptor, γc, or its associated kinase, Jak3, are the major cause of human severe combined immunodeficiency. Although activated by IL-7, Stat5a/b (Stat, signal transducer and activa...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2006-01, Vol.103 (4), p.1000-1005
Main Authors: Yao, Zhengju, Cui, Yongzhi, Watford, Wendy T., Bream, Jay H., Yamaoka, Kunihiro, Hissong, Bruce D., Li, Denise, Durum, Scott K., Jiang, Qiong, Bhandoola, Avinash, Hennighausen, Lothar, O'Shea, John J.
Format: Article
Language:English
Subjects:
Animals
B lymphocytes
B-Lymphocytes - immunology
Biological Sciences
CD8-Positive T-Lymphocytes - virology
Cell Differentiation
Cell Proliferation
Cell Transplantation
Cytokines
Cytokines - metabolism
Developmental biology
Fetus
Flow Cytometry
Hyaluronan Receptors - biosynthesis
Immunology
Janus Kinase 3
Liver
Liver - embryology
Liver cells
Lymphocyte receptors
Lymphocytes - cytology
Mice
Mice, SCID
Mutation
Phenotypes
Protein-Tyrosine Kinases - genetics
Protein-Tyrosine Kinases - metabolism
Receptors, Antigen, T-Cell - metabolism
Receptors, Interleukin-7 - genetics
Reverse Transcriptase Polymerase Chain Reaction
RNA - metabolism
Spleen - embryology
STAT5 Transcription Factor - genetics
STAT5 Transcription Factor - physiology
T lymphocytes
T-Lymphocytes - immunology
T-Lymphocytes - metabolism
Thymocytes
Time Factors
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Summary:Cytokines that use the common gamma chain γc are critical for lymphoid development and function. Mutations of the IL-7 receptor, γc, or its associated kinase, Jak3, are the major cause of human severe combined immunodeficiency. Although activated by IL-7, Stat5a/b (Stat, signal transducer and activator of transcription) have been thought to play limited roles in lymphoid development. However, we now show that mice completely deficient in Stat5a/b have severely impaired lymphoid development and differentiation. Absence of Stat5 also abrogates T cell receptor γ rearrangement and survival of peripheral CD8⁺ T cells. Thus, deficiency of Stat5 results in severe combined immunodeficiency, similar in many respects to deficiency of IL-7R, γc, and Jak3.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0507350103