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Different TCR-induced T lymphocyte responses are potentiated by stiffness with variable sensitivity

Abstract : T cells are mechanosensitive but the effect of stiffness on their functions is still debated. We characterize herein how human primary CD4 + T cell functions are affected by stiffness within the physiological Young's modulus range of 0.5 kPa to 100 kPa. Stiffness modulates T lymphocyte migration and morphological changes induced by TCR/CD3 triggering. Stiffness also increases TCR-induced immune system, metabolism and cell-cycle-related genes. Yet, upon TCR/ CD3 stimulation, while cytokine production increases within a wide range of stiffness, from hundreds of Pa to hundreds of kPa, T cell metabolic properties and cell cycle progression are only increased by the highest stiffness tested (100 kPa). Finally, mechanical properties of adherent antigen-presenting cells modulate cytokine production by T cells. Together, these results reveal that T cells discriminate between the wide range of stiffness values found in the body and adapt their responses accordingly.
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Michael L Saitakis, Stephanie Dogniaux, Christel Goudot, Nathalie L Bufi, Sophie L Asnacios, et al.. Different TCR-induced T lymphocyte responses are potentiated by stiffness with variable sensitivity. eLife, eLife Sciences Publication, 2017, 6, pp.e23190. ⟨10.7554/eLife.23190⟩. ⟨inserm-02446826⟩



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