TY - JOUR
T1 - The contribution of chemokines and migration to the induction of central tolerance in the thymus
AU - Hu, Zicheng
AU - Lancaster, Jessica Naomi
AU - Ehrlich, Lauren I.R.
N1 - Publisher Copyright:
© 2015 Hu, Lancaster and Ehrlich.
PY - 2015
Y1 - 2015
N2 - As T cells develop, they migrate throughout the thymus where they undergo essential bi-directional signaling with stromal cells in distinct thymic microenvironments. Immature thymocyte progenitors are located in the thymic cortex. Following T cell receptor expression and positive selection, thymocytes undergo a dramatic transition: they become rapidly motile and relocate to the thymic medulla. Antigen presenting cells (APCs) within the cortex and medulla display peptides derived from a wide array of self-proteins, which promote thymocyte self-tolerance. If a thymocyte is autoreactive against such antigens, it undergoes either negative selection, via apoptosis, or differentiation into the regulatory T cell lineage. This induction of central tolerance is critical for prevention of autoimmunity. Chemokines and adhesion molecules play an essential role in tolerance induction, as they promote migration of developing thymocytes through the different thymic microenvironments and enhance interactions with APCs displaying self-antigens. Herein, we review the contribution of chemokines and other regulators of thymocyte localization and motility to T cell development, with a focus on their contribution to the induction of central tolerance.
AB - As T cells develop, they migrate throughout the thymus where they undergo essential bi-directional signaling with stromal cells in distinct thymic microenvironments. Immature thymocyte progenitors are located in the thymic cortex. Following T cell receptor expression and positive selection, thymocytes undergo a dramatic transition: they become rapidly motile and relocate to the thymic medulla. Antigen presenting cells (APCs) within the cortex and medulla display peptides derived from a wide array of self-proteins, which promote thymocyte self-tolerance. If a thymocyte is autoreactive against such antigens, it undergoes either negative selection, via apoptosis, or differentiation into the regulatory T cell lineage. This induction of central tolerance is critical for prevention of autoimmunity. Chemokines and adhesion molecules play an essential role in tolerance induction, as they promote migration of developing thymocytes through the different thymic microenvironments and enhance interactions with APCs displaying self-antigens. Herein, we review the contribution of chemokines and other regulators of thymocyte localization and motility to T cell development, with a focus on their contribution to the induction of central tolerance.
KW - Central tolerance
KW - Chemokine receptors
KW - Negative selection
KW - Thymocyte migration
KW - Thymus
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U2 - 10.3389/fimmu.2015.00398
DO - 10.3389/fimmu.2015.00398
M3 - Short survey
AN - SCOPUS:84938539042
SN - 1664-3224
VL - 6
JO - Frontiers in immunology
JF - Frontiers in immunology
IS - JUL
M1 - 398
ER -