Itm2a, a target gene of GATA-3, plays a minimal role in regulating the development and function of T cells.

Tzong-Shyuan Tai,Sung-Yun Pai,I-Cheng Ho,Troy A Baldwin

doi:10.1371/journal.pone.0096535

Abstract

The integral membrane protein 2a (Itm2a) is one of the BRICHOS domain-containing proteins and is structurally related to Itm2b and Itm2c. It is expressed preferentially in the T lineage among hematopoietic cells and is induced by MHC-mediated positive selection. However, its transcriptional regulation and function are poorly understood. Here we showed Itm2a to be a target gene of GATA-3, a T cell-specific transcription factor. Deficiency of Itm2a had little impact on the development and function of polyclonal T cells but resulted in a partial defect in the development of thymocytes bearing a MHC class I-restricted TCR, OT-I. In addition, Itm2a-deficient mice displayed an attenuated T helper cell-dependent immune response in vivo. We further demonstrated that Itm2b but not Itm2c was also expressed in T cells, and was induced upon activation, albeit following a kinetic different from that of Itm2a. Thus, functional redundancy between Itm2a and Itm2b may explain the minimal phenotype of Itm2a deficiency.

Highlights

GATA-3 is the third member of the GATA family of transcription factors [1]
We show that the expression of integral membrane protein 2a (Itm2a) was reduced in GATA-3-deficient thymocytes and that Itm2a is transactivated by GATA-3
The differential expression of Itm2a was subsequently verified with real time PCR, confirming that Itm2a is a GATA-3 target gene in thymocytes (Figure 1A)

Summary

Introduction

GATA-3 is the third member of the GATA family of transcription factors [1]. Among hematopoietic cells, GATA-3 is expressed nearly exclusively in the T lineage, and is critical for the development of CD4+ T helper (Th) cells [2], the differentiation of T helper type 2 (Th2) cells [3,4], the function of regulatory T (Treg) cells [5,6], and the activation/homeostasis of CD8+ cytolytic T (Tc) cells [7,8]. The differential expression of Itm2a was subsequently verified with real time PCR, confirming that Itm2a is a GATA-3 target gene in thymocytes (Figure 1A). Overexpression of GATA-3 in M12 cells, which do not express GATA-3, transactivated a 2kb Itm2a promoter reporter, encompassing the conserved GATA site, as efficiently as an IL-13 promoter (Figure 1C), a known target of GATA-3.

Results

Conclusion