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Interleukin-16 preferentially binds naïve, activated T cells and promotes physiological T cell activation 4660

Year: 2025
Type: article
Abstract: Description Interleukin 16 (IL-16) is a cytokine that is overexpressed in autoimmune diseases and cancer. The function of IL-16 largely remains unknown although chemotaxis and induction of signaling in T cells through interaction with CD4 has been suggested. Here, we work to clarify the role of IL-16 in T cell physiology. To assess IL-16 binding to T cells, resting and activated human peripheral blood mononuclear cells were stained with fluorescently labeled IL-16 and evaluated by flow cytometry. Resting CD4 and CD8 T cells showed only minimal binding to IL-16, questioning the proposed high-affinity interaction between IL-16 and CD4. In contrast, IL-16 efficiently bound to activated CD4+ and CD8+ T cells, with T cell subsets showing differential levels of binding to IL-16 (TN > TCM > TEM > TEMRA). While T cells required prior activation to bind IL-16, the level of activation did not correlate with IL-16 binding. In mixed lymphocyte reactions using splenocytes from MHC-mismatched C57BL/6 mice, we found that addition of recombinant IL-16 significantly increased T cell activation but not IL-2 secretion. Experiments are ongoing to determine the molecular mechanism behind IL-16-mediated T cell activation and to further delineate the phenotype of IL-16-binding T cells in order to guide identification of alternative receptors for IL-16. This work will inform future therapeutic strategies targeting IL-16 in autoimmune diseases and cancer. Funding Sources Supported by NIAID T32AI095190; Maryland Department of Health’s Cigarette Restitution Fund Program (CH-649-CRF). Topic Categories Cytokines and Chemokines and Their Receptors (CCR)
DOI: 10.1093/jimmun/vkaf283.2308
Language: English
Subfield: Immunology
Open Access status: bronze
OpenAlex ID: W4416449502
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