Phospholipase Cγ1 is essential for T cell development, activation, and tolerance

Author:

Fu Guoping1,Chen Yuhong1,Yu Mei12,Podd Andy13,Schuman James13,He Yinghong12,Di Lie1,Yassai Maryam1,Haribhai Dipica4,North Paula E.5,Gorski Jack13,Williams Calvin B.4,Wang Demin13,Wen Renren1

Affiliation:

1. The Blood Research Institute, Blood Center of Wisconsin, Milwaukee, WI 53226

2. State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 225001, China

3. Department of Microbiology and Molecular Genetics, Medical College of Wisconsin Milwaukee, WI 53226

4. Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226

5. Department of Pathology and Laboratory Medicine, Children’s Hospital of Wisconsin, Milwaukee, WI 53226

Abstract

Phospholipase Cγ1 (PLCγ1) is an important signaling effector of T cell receptor (TCR). To investigate the role of PLCγ1 in T cell biology, we generated and examined mice with T cell–specific deletion of PLCγ1. We demonstrate that PLCγ1 deficiency affects positive and negative selection, significantly reduces single-positive thymocytes and peripheral T cells, and impairs TCR-induced proliferation and cytokine production, and the activation of ERK, JNK, AP-1, NFAT, and NF-κB. Importantly, PLCγ1 deficiency impairs the development and function of FoxP3+ regulatory T cells, causing inflammatory/autoimmune symptoms. Therefore, PLCγ1 is essential for T cell development, activation, and tolerance.

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

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