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- W4313381844 abstract "Abstract Immune homeostasis is maintained by tolerogenic & immunogenic subsets of cells. They determine the intensity & type of response to infection & vaccination. Loss of tolerance results activation of self-reactive T-cells that attack self-tissues & develop pathologic conditions like arthritis. An important mechanism by which tolerance is maintained in periphery is by induction of regulatory T-cells (TREG). Collagen induced arthritis (CIA) is a well-established model of rheumatoid arthritis. Immunization with collagen in presence of adjuvant in mice leads to production of proinflammatory cytokines, which leads to bone erosion by osteoclasts. Our laboratory has shown that osteoclasts function as antigen presenting cells (APCs), which induce FOXP3 in CD8+ T-cell (OC-iTcREG). Previous studies demonstrated that OC-iTcREG limit bone resorption in murine osteoporosis. We have also identified that, osteoclast express Notch ligand DLL4 & use Notch signaling to induce FOXP3 in CD8 T-cells. Expression of Notch ligand is also observed on other APCs, which we hypothesize are tolerogenic. Thus, we will characterize & examine whether these tolerogenic APCs can induce TREG & re-establish tolerance. We will present the results using adoptive transfer experiments, to measure immunomodulatory activity of DLL4 expressing APCs in CIA model. Efficacy of the treatment will be assessed by studying serum CTX, proinflammatory cytokines, immune-phenotypes of T-cell & APC subtypes from joint tissues of mice. Further, effect of these tolerogenic APCs will be compared with conventional APCs in CIA model to assess its therapeutic potential. This study will help to understand the complex interplay of tolerogenic cells in re-establishing immune homeostasis." @default.
- W4313381844 created "2023-01-06" @default.
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- W4313381844 date "2018-05-01" @default.
- W4313381844 modified "2023-09-27" @default.
- W4313381844 title "Disruption of self-tolerance in autoimmune diseases and therapeutic modulation to restore immune balance" @default.
- W4313381844 doi "https://doi.org/10.4049/jimmunol.200.supp.175.12" @default.
- W4313381844 hasPublicationYear "2018" @default.
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