Piezo1 channels restrain regulatory T cells but are dispensable for effector CD4+ T cell responses

Amit Jairaman; Shivashankar Othy; Joseph L Dynes; Andriy V Yeromin; Angel Zavala; Milton L Greenberg; Jamison L Nourse; Jesse R Holt; Stuart M Cahalan; Francesco Marangoni; Ian Parker; Medha M Pathak; Michael D Cahalan

doi:10.1126/sciadv.abg5859

Piezo1 channels restrain regulatory T cells but are dispensable for effector CD4⁺ T cell responses

Sci Adv. 2021 Jul 7;7(28):eabg5859. doi: 10.1126/sciadv.abg5859. Print 2021 Jul.

Authors

Amit Jairaman¹, Shivashankar Othy¹, Joseph L Dynes¹, Andriy V Yeromin¹, Angel Zavala¹, Milton L Greenberg¹, Jamison L Nourse^{1

2}, Jesse R Holt^{1

2}, Stuart M Cahalan^{3

4}, Francesco Marangoni¹, Ian Parker^{1

5}, Medha M Pathak^{1

2

6

7}, Michael D Cahalan^{8

9}

Affiliations

¹ Department of Physiology and Biophysics, University of California, Irvine, CA 92697-4561, USA.
² Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, CA 92697, USA.
³ Howard Hughes Medical Institute, Department of Neuroscience, The Scripps Research Institute, La Jolla, CA 92037, USA.
⁴ Vertex Pharmaceuticals, 3215 Merryfield Row, San Diego, CA 92121, USA.
⁵ Department of Neurobiology and Behavior, University of California, Irvine, CA 92697, USA.
⁶ Department of Biomedical Engineering, University of California, Irvine, CA 92697, USA.
⁷ Center for Complex Systems Biology, University of California, Irvine, CA 92697, USA.
⁸ Department of Physiology and Biophysics, University of California, Irvine, CA 92697-4561, USA. [email protected].
⁹ Institute for Immunology, University of California, Irvine, CA 92697, USA.

Abstract

T lymphocytes encounter complex mechanical cues during an immune response. The mechanosensitive ion channel, Piezo1, drives inflammatory responses to bacterial infections, wound healing, and cancer; however, its role in helper T cell function remains unclear. In an animal model for multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), we found that mice with genetic deletion of Piezo1 in T cells showed diminished disease severity. Unexpectedly, Piezo1 was not essential for lymph node homing, interstitial motility, Ca²⁺ signaling, T cell proliferation, or differentiation into proinflammatory T helper 1 (T_H1) and T_H17 subsets. However, Piezo1 deletion in T cells resulted in enhanced transforming growth factor-β (TGFβ) signaling and an expanded pool of regulatory T (T_reg) cells. Moreover, mice with deletion of Piezo1 specifically in T_reg cells showed significant attenuation of EAE. Our results indicate that Piezo1 selectively restrains T_reg cells, without influencing activation events or effector T cell functions.

Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Differentiation
Encephalomyelitis, Autoimmune, Experimental* / pathology
Ion Channels / genetics
Lymphocyte Activation
Mice
Mice, Inbred C57BL
Multiple Sclerosis*
T-Lymphocytes, Regulatory
Th1 Cells

Substances

Ion Channels
Piezo1 protein, mouse

Abstract

Publication types

MeSH terms

Substances

Grants and funding