Peripherally Induced Tolerance Depends on Peripheral Regulatory T Cells That Require Hopx To Inhibit Intrinsic IL-2 Expression
Andrew Jones,Adeleye Opejin,Jacob G. Henderson,Cindy Gross,Rajan Jain,Jonathan A. Epstein,Richard A. Flavell,Daniel Hawiger +7 more
TLDR
It is reported that Hopx+ pTregs converted by DCs from Hopx− T cells are indispensible to sustain tolerance that prevents autoimmune responses directed at self-Ags during experimental acute encephalomyelitis and thatHopx inhibits intrinsic IL-2 expression in pT Regs after antigenic rechallenge.Abstract:
Dendritic cells (DCs) can induce peripheral immune tolerance that prevents autoimmune responses. Ag presentation by peripheral DCs under steady-state conditions leads to a conversion of some peripheral CD4(+) T cells into regulatory T cells (Tregs) that require homeodomain-only protein (Hopx) to mediate T cell unresponsiveness. However, the roles of these peripheral Tregs (pTregs) in averting autoimmune responses, as well as immunological mechanisms of Hopx, remain unknown. We report that Hopx(+) pTregs converted by DCs from Hopx(-) T cells are indispensible to sustain tolerance that prevents autoimmune responses directed at self-Ags during experimental acute encephalomyelitis. Our studies further reveal that Hopx inhibits intrinsic IL-2 expression in pTregs after antigenic rechallenge. In the absence of Hopx, increased levels of IL-2 lead to death and decreased numbers of pTregs. Therefore, formation of Hopx(+) pTregs represents a crucial pathway of sustained tolerance induced by peripheral DCs, and the maintenance of such pTregs and tolerance requires functions of Hopx to block intrinsic IL-2 production in pTregs.read more
Citations
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Dendritic Cells As Inducers of Peripheral Tolerance.
TL;DR: In this paper, the essential roles of dendritic cells in orchestrating mechanisms of peripheral T cell tolerance as determined by targeted delivery of defined antigens to DCs in vivo in combination with various genetic modifications of DCs.
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Immunomodulatory Functions of BTLA and HVEM Govern Induction of Extrathymic Regulatory T Cells and Tolerance by Dendritic Cells.
Andrew Jones,Jessica Bourque,Lindsey M. Kuehm,Adeleye Opejin,Ryan M. Teague,Cindy Gross,Daniel Hawiger +6 more
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Natural and Induced Tolerogenic Dendritic Cells.
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Immunomodulatory Bonds of the Partnership between Dendritic Cells and T Cells
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TL;DR: This comprehensive review details the most successful drugs in MS therapy and focuses on nanomedicine-based drug delivery approaches of biological immunomodulatory mediators for the treatment of multiple sclerosis.
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