Itm2a, a target gene of GATA-3, plays a minimal role in regulating the development and function of T cells.
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.
Division of Rheumatology, Immunology, and Allergy, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States of America; Harvard Medical School, Boston, Massachusetts, United States of America; Department of Medical Research, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan.
Tzong-Shyuan
TS
Tai
Harvard Medical School, Boston, Massachusetts, United States of America; Division of Pediatric Hematology-Oncology, Department of Pediatrics, Children's Hospital Boston, Boston, Massachusetts, United States of America; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America.
Sung-Yun
SY
Pai
Division of Rheumatology, Immunology, and Allergy, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States of America; Harvard Medical School, Boston, Massachusetts, United States of America.
I-Cheng
IC
Ho
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D050990:GATA3 Transcription Factor / Q000378:metabolism*; D005786:Gene Expression Regulation; D007111:Immunity, Cellular; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D017434:Protein Structure, Tertiary; D013601:T-Lymphocytes / Q000166:cytology*; D060168:Thymocytes / Q000166:cytology*
D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; C117398:Itm2a protein, mouse; D008565:Membrane Proteins