Intercellular Protein Transfer from Thymocytes to Thymic Epithelial Cells.

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2016

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Abstract

Promiscuous expression of tissue restricted antigens (TRAs) in medullary thymic epithelial cells (mTECs) is crucial for negative selection of self-reactive T cells to establish central tolerance. Intercellular transfer of self-peptide-MHC complexes from mTECs to thymic dendritic cells (DCs) allows DCs to acquire TRAs, which in turn contributes to negative selection and regulatory T cell generation. However, mTECs are unlikely to express all TRAs, such as immunoglobulins generated only in B cells after somatic recombination, hyper-mutation, or class-switches. We report here that both mTECs and cortical TECs can efficiently acquire not only cell surface but also intracellular proteins from thymocytes. This reveals a previously unappreciated intercellular sharing of molecules from thymocytes to TECs, which may broaden the TRA inventory in mTECs for establishing a full spectrum of central tolerance.

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10.1371/journal.pone.0152641

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Wang, Hong-Xia, Yu-Rong Qiu and Xiao-Ping Zhong (2016). Intercellular Protein Transfer from Thymocytes to Thymic Epithelial Cells. PLoS One, 11(3). p. e0152641. 10.1371/journal.pone.0152641 Retrieved from https://hdl.handle.net/10161/11812.

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Scholars@Duke

Zhong

Xiaoping Zhong

Professor of Pediatrics

The immune system protects the host from microbial infection but can cause diseases if not properly controlled. My lab is interested in the receptor signaling mediated regulation of immune cell development and function as well as the pathogenesis and treatment of autoimmune diseases and allergies.

We are currently investigating the roles diacylglycerol kinases (DGKs) and TSC1/2-mTOR play in the immune system. DGKs are a family of ten enzymes that catalyze the conversion of diacylglycerol (DAG) to phosphatidic acid (PA), Both DAG and PA are important second messengers involved signaling from numerous receptors. While we expect DGKs to perform important roles in development and cellular function by modulating DAG and PA levels, the physiologic functions of DGKs have been poorly understood. Using cell line models and genetically manipulated mice, we have demonstrated that DGKα and ζ isoforms play critical roles in: T cell development, activation, and anergy by regulating T cell receptor signaling; FcεRI signaling and mast cell function; and Toll-like receptor signaling and innate immune responses.

Research areas that we are actively pursuing include:
1. The mechanisms that control T cell maturation, activation
and self-tolerance.
2. NKT cell development and function.
3. Thymic epithelial cells and thymic development, function, and involution.
4. Regulation of Toll-like receptor signaling and innate immunity. 
5. The pathogenesis and treatment of autoimmune hepatitis. 
6. Mast cell development and function.
7. The pathogenesis and immunotherapy for peanut allergy.


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