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Collagen fiber structure guides 3D motility of cytotoxic T lymphocytes.

Publication ,  Journal Article
Pruitt, HC; Lewis, D; Ciccaglione, M; Connor, S; Smith, Q; Hickey, JW; Schneck, JP; Gerecht, S
Published in: Matrix biology : journal of the International Society for Matrix Biology
January 2020

Lymphocyte motility is governed by a complex array of mechanisms, and highly dependent on external microenvironmental cues. Tertiary lymphoid sites in particular have unique physical structure such as collagen fiber alignment, due to matrix deposition and remodeling. Three dimensional studies of human lymphocytes in such environments are lacking. We hypothesized that aligned collagenous environment modulates CD8+ T cells motility. We encapsulated activated CD8+ T cells in collagen hydrogels of distinct fiber alignment, a characteristic of tumor microenvironments. We found that human CD8+ T cells move faster and more persistently in aligned collagen fibers compared with nonaligned collagen fibers. Moreover, CD8+ T cells move along the axis of collagen alignment. We showed that myosin light chain kinase (MLCK) inhibition could nullify the effect of aligned collagen on CD8+ T cell motility patterns by decreasing T cell turning in unaligned collagen fiber gels. Finally, as an example of a tertiary lymphoid site, we found that xenograft prostate tumors exhibit highly aligned collagen fibers. We observed CD8+ T cells alongside aligned collagen fibers, and found that they are mostly concentrated in the periphery of tumors. Overall, using an in vitro controlled hydrogel system, we show that collagen fiber organization modulates CD8+ T cells movement via MLCK activation thus providing basis for future studies into relevant therapeutics.

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Published In

Matrix biology : journal of the International Society for Matrix Biology

DOI

EISSN

1569-1802

ISSN

0945-053X

Publication Date

January 2020

Volume

85-86

Start / End Page

147 / 159

Related Subject Headings

  • T-Lymphocytes, Cytotoxic
  • Prostatic Neoplasms
  • Neoplasm Transplantation
  • Myosin-Light-Chain Kinase
  • Mice
  • Male
  • Lab-On-A-Chip Devices
  • Humans
  • Extracellular Matrix
  • Collagen
 

Citation

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Pruitt, H. C., Lewis, D., Ciccaglione, M., Connor, S., Smith, Q., Hickey, J. W., … Gerecht, S. (2020). Collagen fiber structure guides 3D motility of cytotoxic T lymphocytes. Matrix Biology : Journal of the International Society for Matrix Biology, 8586, 147–159. https://doi.org/10.1016/j.matbio.2019.02.003
Pruitt, Hawley C., Daniel Lewis, Mark Ciccaglione, Sydney Connor, Quinton Smith, John W. Hickey, Jonathan P. Schneck, and Sharon Gerecht. “Collagen fiber structure guides 3D motility of cytotoxic T lymphocytes.Matrix Biology : Journal of the International Society for Matrix Biology 85–86 (January 2020): 147–59. https://doi.org/10.1016/j.matbio.2019.02.003.
Pruitt HC, Lewis D, Ciccaglione M, Connor S, Smith Q, Hickey JW, et al. Collagen fiber structure guides 3D motility of cytotoxic T lymphocytes. Matrix biology : journal of the International Society for Matrix Biology. 2020 Jan;85–86:147–59.
Pruitt, Hawley C., et al. “Collagen fiber structure guides 3D motility of cytotoxic T lymphocytes.Matrix Biology : Journal of the International Society for Matrix Biology, vol. 85–86, Jan. 2020, pp. 147–59. Epmc, doi:10.1016/j.matbio.2019.02.003.
Pruitt HC, Lewis D, Ciccaglione M, Connor S, Smith Q, Hickey JW, Schneck JP, Gerecht S. Collagen fiber structure guides 3D motility of cytotoxic T lymphocytes. Matrix biology : journal of the International Society for Matrix Biology. 2020 Jan;85–86:147–159.
Journal cover image

Published In

Matrix biology : journal of the International Society for Matrix Biology

DOI

EISSN

1569-1802

ISSN

0945-053X

Publication Date

January 2020

Volume

85-86

Start / End Page

147 / 159

Related Subject Headings

  • T-Lymphocytes, Cytotoxic
  • Prostatic Neoplasms
  • Neoplasm Transplantation
  • Myosin-Light-Chain Kinase
  • Mice
  • Male
  • Lab-On-A-Chip Devices
  • Humans
  • Extracellular Matrix
  • Collagen