Journal
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
Volume 106, Issue 12, Pages 3001-3008Publisher
WILEY
DOI: 10.1002/jbm.a.36489
Keywords
regulatory T cells; substrate rigidity; poly(dimethylsiloxane); T-cell immunotherapy; Mechanosensing
Funding
- National Center for Advancing Translational Sciences, National Institutes of Health [UL1TR000040]
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, NATIONAL INSTITUTE OF HEALTH [R01AI110593U24AI118669]
- NSF Graduate Research Fellowships Program (GRFP)
- NSF GRFP
- NIH [UL1TR000040, U24AI118669]
- NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES [UL1TR000040] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [F32AI100496, R01AI110593, U24AI118669] Funding Source: NIH RePORTER
Ask authors/readers for more resources
The immune system maintains a balance between protection and tolerance. Regulatory T cells (Tregs) function as a vital tolerance mechanism in the immune system to suppress effector immune cells. Additionally, Tregs can be utilized as a form of immunotherapy for autoimmune disorders. As T cells have previously been shown to exhibit sensitivity to the rigidity of an activating substrate upon activation via IL-2 secretion, we herein explore the previously unknown effect of substrate rigidity on the induction of Tregs from conventional naive mouse CD4(+) T cells. Substrates with modulatable rigidities ranging from a hundred kilopascals to a few megapascals were fabricated via poly(dimethylsiloxane). We found that there was a significant increase in Treg induction at lower substrate rigidities (i.e., E similar to 100 kPa) compared to higher rigidity levels (i.e., E similar to 3 MPa). To confirm that this significant difference in induction rate was truly related to T-cell mechanosensing, we administered compound Y-27632 to inhibit myosin contractility. In the presence of Y-27632, the myosin-based contractility was disrupted and, as a result, the difference in Treg induction caused by the substrate rigidity was abrogated. This study demonstrates that mechanosensing is involved in Treg induction and raises questions about the underlying molecular mechanisms involved in this process. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 3001-3008, 2018.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available