Chan-Wang J Lio

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Recognition of self-antigens is required for regulatory T (Treg) cells to exert dominant tolerance. However, the mechanism by which self-reactive thymocytes are diverted into the Treg cell subset is unclear. To address this question, we looked for the immediate precursors to Treg cells within Foxp3(-)CD4+CD8(-) thymocytes. By using intrathymic transfer, we(More)
Appropriate development of regulatory T (Treg) cells is necessary to prevent autoimmunity. Neonatal mice, unlike adults, lack factors required for Treg cell development. It is unclear what these missing factors are. However, signals emanating from the T cell receptor (TCR), the costimulatory receptor CD28, and the family of gammac-dependent cytokine(More)
The instruction of the immune system to be tolerant of self, thereby preventing autoimmunity, is facilitated by the education of T cells in a specialized organ, the thymus, in which self-reactive cells are either eliminated or differentiated into tolerogenic Foxp3(+) regulatory T (T(reg)) cells. However, it is unknown whether T cells are also educated to be(More)
The generation of regulatory T (T(Reg)) cells in the thymus is crucial for immune homeostasis and self-tolerance. Recent discoveries have revealed the cellular and molecular mechanisms that govern the differentiation of a subset of developing thymocytes into natural T(Reg) cells. Several models, centred on the self-reactivity of the T cell receptor (TCR),(More)
Because the deletion of self-reactive T cells is incomplete, thymic development of natural Foxp3+CD4+ regulatory T cells (Treg cells) is required for preventing autoimmunity. However, the function of T cell antigen receptor (TCR) specificity in thymic Treg cell development remains controversial. To address this issue, we generated a transgenic line(More)
The discovery of Ten Eleven Translocation proteins, enzymes that oxidize 5-methylcytosine (5mC) in DNA, has revealed novel mechanisms for the regulation of DNA methylation. We have mapped 5-hydroxymethylcytosine (5hmC) at different stages of T-cell development in the thymus and T-cell differentiation in the periphery. We show that 5hmC is enriched in the(More)
The contribution of thymic antigen-presenting-cell (APC) subsets in selecting a self-tolerant T cell population remains unclear. We show that bone marrow (BM) APCs and medullary thymic epithelial cells (mTECs) played nonoverlapping roles in shaping the T cell receptor (TCR) repertoire by deletion and regulatory T (Treg) cell selection of distinct TCRs.(More)
The T cell costimulatory molecule CD28 plays an important role in the thymic generation of Foxp3(+) regulatory T cells (Tregs) essential for the maintenance of self-tolerance. In this study, we show that a cell-intrinsic signal from CD28 is involved in the generation of cytokine-responsive Foxp3(-) precursors using studies of mixed bone marrow chimeras as(More)
Chemokines promote lymphocyte motility by triggering F-actin rearrangements and inducing cellular polarization. Chemokines can also enhance cell-cell adhesion and costimulate T cells. In this study, we establish a requirement for the actin-bundling protein L-plastin (LPL) in CCR7- and sphingosine-1-phosphate-mediated T cell chemotaxis using LPL(-/-) mice.(More)
The generation of Foxp3(+) regulatory T (Treg) cells in the thymus is essential for immune homeostasis. In the past several years, substantial progress has been made in understanding the mechanisms by which a minor portion of developing thymocytes are selected to become Treg cells. Although previously controversial, recent data support the importance of TCR(More)