Stat5a/b Are Essential for Normal Lymphoid Development and Differentiation

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2006 Jan 19

PMID 16418296

Citations 214

Authors

Zhengju Yao

Yongzhi Cui

Wendy T Watford

Jay H Bream

Kunihiro Yamaoka

Bruce D Hissong

Denise Li

Scott K Durum

Qiong Jiang

Avinash Bhandoola

Lothar Hennighausen

John J OShea

Affiliations

Soon will be listed here.

Abstract

Cytokines that use the common gamma chain gammac are critical for lymphoid development and function. Mutations of the IL-7 receptor, gammac, 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 gamma 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, gammac, and Jak3.

Citing Articles

STAT5B leukemic mutations, altering SH2 tyrosine 665, have opposing impacts on immune gene programs.

Lee H, Chen J, Philips R, Lee S, Feng X, Wu Z bioRxiv. 2025; .

PMID: 39803507 PMC: 11722272. DOI: 10.1101/2024.12.20.629685.

Maintenance of hematopoietic stem cells by tyrosine-unphosphorylated STAT5 and JAK inhibition.

Williams M, Wang X, Bastos H, Grondys-Kotarba G, Wu Q, Jin S Blood Adv. 2024; 9(2):291-309.

PMID: 39374575 PMC: 7617191. DOI: 10.1182/bloodadvances.2024014046.

Tyrosine phosphorylation of both STAT5A and STAT5B is necessary for maximal IL-2 signaling and T cell proliferation.

Lin J, Ge M, Liu C, Holewinski R, Andresson T, Yu Z Nat Commun. 2024; 15(1):7372.

PMID: 39191751 PMC: 11349758. DOI: 10.1038/s41467-024-50925-6.

Interaction of the intestinal cytokines-JAKs-STAT3 and 5 axes with RNA N6-methyladenosine to promote chronic inflammation-induced colorectal cancer.

Esmaeili N, Bakheet A, Tse W, Liu S, Han X Front Oncol. 2024; 14:1352845.

PMID: 39136000 PMC: 11317299. DOI: 10.3389/fonc.2024.1352845.

STAT5B SH2 variants disrupt mammary enhancers and the stability of genetic programs during pregnancy.

Lee H, Liu C, Hennighausen L bioRxiv. 2024; .

PMID: 38903072 PMC: 11188103. DOI: 10.1101/2024.05.06.592736.

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