Receptor signaling in immune cell development and function
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Receptor signaling in immune cell development and function Xiao-Ping Zhong • Jinwook Shin • Balachandra K. Gorentla • Tommy O’Brien Sruti Srivatsan • Li Xu • Yong Chen • Danli Xie • Hongjie Pan
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Published online: 3 December 2010 Ó Springer Science+Business Media, LLC 2010
Abstract Immune cell development and function must be tightly regulated through cell surface receptors to ensure proper responses to pathogen and tolerance to self. In T cells, the signal from the T-cell receptor is essential for T-cell maturation, homeostasis, and activation. In mast cells, the high-affinity receptor for IgE transduces signal that promotes mast cell survival and induces mast cell activation. In dendritic cells and macrophages, the toll-like receptors recognize microbial pathogens and play critical roles for both innate and adaptive immunity against pathogens. Our research explores how signaling from these receptors is transduced and regulated to better understand these immune cells. Our recent studies have revealed diacylglycerol kinases and TSC1/2-mTOR as critical signaling molecules/regulators in T cells, mast cells, dendritic cells, and macrophages. Keywords T-cell receptor T-cell development Anergy Regulatory T cells Dendritic cell (DC) Macrophages Mast cells Toll-like receptor (TLR) FceRI Diacylglycerol kinase (DGK) Mammalian target of rapamycin (mTOR) Tuberous sclerosis 1
Regulating T-cell receptor signaling for T-cell development and function During T-cell maturation in the thymus, a functional T-cell receptor (TCR) is generated through proper V(D)J recombination [1]. Proper TCR signaling is critical for T-cell maturation and survival. Absence of the pre-TCR or the TCR signal results in developmental blockage at the CD4-CD8- double negative (DN) stage and CD4?CD8? double X.-P. Zhong J. Shin B. K. Gorentla T. O’Brien S. Srivatsan L. Xu Y. Chen D. Xie H. Pan Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA X.-P. Zhong T. O’Brien S. Srivatsan Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA X.-P. Zhong (&) Department of Pediatrics-Allergy and Immunology, Duke University Medical Center, Box 2644, Durham, NC 27710, USA e-mail: [email protected]
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positive (DP) stage, respectively [2–4]. In addition, the strength of TCR signal influences the outcome of thymic selections. DP thymocytes expressing TCRs with high affinities to self-peptide MHC complexes are negatively selected due to programmed cell death. Negative selection deletes highly self-reactive T cells to establish central tolerance. Thymocytes express TCRs with low and moderate affinities to self-peptide-MHC complexes are positively selected to mature [5]. Proper thymic selection is critical for generating a repertoire T cells for effective immune responses against foreign antigens and, at the same time, self-tolerant. Furthermore, specialized TCRs such as the cdTCR and the invariant Va14 Ja18 TCR in mouse may transduce sig
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