This study investigates the role of tert-Butylhydroquinone (tBHQ) and steroids inregulating IL17D expression in fibroblasts, fibrosarcoma cell lines, and melanoma, alongside examining IL17D's influence on fibroblast migration, macrophage antigen presentation, and the presence of TGF-beta 1 protein in fibroblast supernatant. My findings reveal a differential induction of IL17D across cell types and treatment conditions. Specifically, tBHQ significantly induces IL17D in primary fibroblasts but not in fibrosarcoma or melanoma cells, where hydrocortisone instead prompts IL17D expression. This suggests a context-dependent regulation of IL17D, potentially impacting disease progression or treatment responses.

Further, IL17D enhances migration in both fibroblasts and D29M1 fibrosarcomacells, suggesting a role of IL17D in cell motility. In macrophages, IL17D downregulates genes of antigen presentation, as the evidence of the immunomodulatory effects of IL17D, particularly under inflammation. Additionally, the absence of TGF-beta 1 in IL17D knockout fibroblast supernatant unveils a regulatory function of IL17D in cell migration and in the microenvironment of cell migration.

Overall, my study highlights the multifaceted roles of IL17D in cell biology andimmunology, offering insights into its potential as a therapeutic target in cancer and immune diseases. Further research is necessary to unravel the complex mechanisms through which IL17D influences cell behavior and immune responses, which could pave the way for innovative treatments.

Nonobese diabetic (NOD) mice, a model of insulin-dependent diabetes mellitus, have a defect in natural killer (NK) cell-mediated functions. Here we show impairment in an activating receptor, NKG2D, in NOD NK cells. While resting NK cells from C57BL/6 and NOD mice expressed equivalent levels of NKG2D, upon activation NOD NK cells but not C57BL/6 NK cells expressed NKG2D ligands, which resulted in downmodulation of the receptor. NKG2D-dependent cytotoxicity and cytokine production were decreased because of receptor modulation, accounting for the dysfunction. Modulation of NKG2D was mostly dependent on the YxxM motif of DAP10, the NKG2B-associated adaptor that activates phosphoinositide 3 kinase. These results suggest that NK cells may be desensitized by exposure to NKG2D ligands.

Nonobese diabetic (NOD) mice, a model of insulin-dependent diabetes mellitus, have a defect in natural killer (NK) cell-mediated functions. Here we show impairment in an activating receptor, NKG2D, in NOD NK cells. While resting NK cells from C57BL/6 and NOD mice expressed equivalent levels of NKG2D, upon activation NOD NK cells but not C57BL/6 NK cells expressed NKG2D ligands, which resulted in downmodulation of the receptor. NKG2D-dependent cytotoxicity and cytokine production were decreased because of receptor modulation, accounting for the dysfunction. Modulation of NKG2D was mostly dependent on the YxxM motif of DAP10, the NKG2D-associated adaptor that activates phosphoinositide 3 kinase. These results suggest that NK cells may be desensitized by exposure to NKG2D ligands.