PhD Research Summary - Dr. Baeke
T lymphocytes are central players in immune defense but can also drive autoimmune diseases such as type 1 diabetes (T1D). The active form of vitamin D, 1,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃], and its structural analogs are known to modulate immune responses, preventing T1D in non-obese diabetic mice by dampening inflammatory T cell activity and promoting regulatory T cell (Treg) responses.
In her PhD research, Dr. Baeke investigated whether these effects arise from direct actions on T cells themselves. She developed an optimized in vitro model using human primary T lymphocytes and demonstrated that the vitamin D analog TX527 directly modulates T cell activation, proliferation, and cytokine production while inducing a functional regulatory T cell phenotype with anti-inflammatory and tissue-targeting properties.
Further, Dr. Baeke explored combination therapies involving TX527, anti-CD3 antibodies, and cyclosporine A (CsA) in NOD mice. The triple low-dose combination effectively prevented autoimmune recurrence of diabetes after islet transplantation, outperforming individual or dual treatments.
This work identifies T cells as direct targets of active vitamin D and its analogs and supports the use of vitamin D analogs as dose-reducing agents in combination immunotherapies for autoimmune diseases.
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