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Different TCR-induced T lymphocyte responses are potentiated by stiffness with variable sensitivity
Michael Saitakis1, Stéphanie Dogniaux1, Christel Goudot1
1Institut Curie Section Recherche, INSERM U932 & PSL Research University, Paris, France.
Elife
|June 9, 2017
Summary
T cells sense tissue stiffness, impacting their migration, gene expression, and cytokine production. High stiffness specifically enhances T cell metabolism and proliferation, showing cells adapt to their mechanical environment.
Area of Science:
- Immunology
- Cell Biology
- Biophysics
Background:
- T cells are known to be mechanosensitive, but the precise impact of substrate stiffness on their diverse functions remains incompletely understood.
- Understanding these mechanical influences is crucial for comprehending T cell behavior in various physiological and pathological contexts.
Purpose of the Study:
- To investigate how varying substrate stiffness, within the physiological range (0.5 kPa to 100 kPa), affects human primary CD4+ T cell functions.
- To determine the specific thresholds of stiffness that modulate T cell migration, gene expression, metabolism, cell cycle progression, and cytokine production.
Main Methods:
- Human primary CD4+ T cells were cultured on substrates with controlled stiffness ranging from 0.5 kPa to 100 kPa.
- T cell migration, morphology, gene expression (immune system, metabolism, cell cycle), cytokine production, and metabolic properties were analyzed following T cell receptor/CD3 (TCR/CD3) triggering.
- The influence of antigen-presenting cell mechanical properties on T cell cytokine production was also assessed.
Main Results:
- Substrate stiffness modulated T lymphocyte migration and morphology upon TCR/CD3 stimulation.
- TCR/CD3 triggering increased immune system, metabolism, and cell-cycle-related genes across a range of stiffness values.
- While cytokine production increased broadly with stiffness, enhanced T cell metabolism and cell cycle progression were observed only at the highest stiffness (100 kPa).
- Mechanical properties of antigen-presenting cells influenced T cell cytokine production.
Conclusions:
- Human primary CD4+ T cells exhibit distinct responses to a wide spectrum of physiological stiffness values.
- T cells adapt their functions, including migration, gene expression, metabolism, and proliferation, in response to mechanical cues.
- These findings highlight the importance of the mechanical microenvironment in regulating T cell-mediated immunity.
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