Investigations on T cell transmigration in a human skin-on-chip (SoC) model

Lab on a Chip ◽  
2021 ◽  
Vol 21 (8) ◽  
pp. 1527-1539
Author(s):  
Xiaoou Ren ◽  
Anthony E. Getschman ◽  
Samuel Hwang ◽  
Brian F. Volkman ◽  
Thomas Klonisch ◽  
...  
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
Human Skin ◽  
Drug Candidates ◽  
New Drug ◽  
Human T Lymphocytes ◽  
Quantitative Studies ◽  
Inflammatory Skin ◽  
Skin Conditions ◽  
On Chip

Our skin-on-chip (SoC) model uniquely enabled quantitative studies of transendothelial and transepithelial migration of human T lymphocytes under mimicked inflammatory skin conditions and was used to test new drug candidates.

scholarly journals Fisetin, a 3,7,3′,4′-Tetrahydroxyflavone Inhibits the PI3K/Akt/mTOR and MAPK Pathways and Ameliorates Psoriasis Pathology in 2D and 3D Organotypic Human Inflammatory Skin Models

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 1089 ◽  
Author(s):  
Jean Christopher Chamcheu ◽  
Stephane Esnault ◽  
Vaqar M. Adhami ◽  
Andrea L. Noll ◽  
Sergette Banang-Mbeumi ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Human Skin ◽  
Mononuclear Cells ◽  
Psoriatic Skin ◽  
Epidermal Keratinocytes ◽  
Human Epidermal Keratinocytes ◽  
Peripheral Blood Mononuclear ◽  
Inflammatory Skin ◽  
2D And 3D

Psoriasis is a chronic immune-mediated skin disease that involves the interaction of immune and skin cells, and is characterized by cytokine-driven epidermal hyperplasia, deviant differentiation, inflammation, and angiogenesis. Because the available treatments for psoriasis have significant limitations, dietary products are potential natural sources of therapeutic molecules, which can repair the molecular defects associated with psoriasis and could possibly be developed for its management. Fisetin (3,7,3′,4′-tetrahydroxyflavone), a phytochemical naturally found in pigmented fruits and vegetables, has demonstrated proapoptotic and antioxidant effects in several malignancies. This study utilized biochemical, cellular, pharmacological, and tissue engineering tools to characterize the effects of fisetin on normal human epidermal keratinocytes (NHEKs), peripheral blood mononuclear cells (PBMC), and CD4+ T lymphocytes in 2D and 3D psoriasis-like disease models. Fisetin treatment of NHEKs dose- and time-dependently induced differentiation and inhibited interleukin-22-induced proliferation, as well as activation of the PI3K/Akt/mTOR pathway. Fisetin treatment of TNF-α stimulated NHEKs also significantly inhibited the activation of p38 and JNK, but had enhanced effect on ERK1/2 (MAPK). In addition, fisetin treatment significantly decreased the secretion of Th1/Th-17 pro-inflammatory cytokines, particularly IFN-γ and IL-17A by 12-O-tetradecanolylphorbol 13-acetate (TPA)-stimulated NHEKs and anti-CD3/CD28-activated human PBMCs. Furthermore, we established the in vivo relevance of fisetin functions, using a 3D full-thickness human skin model of psoriasis (FTRHSP) that closely mimics in vivo human psoriatic skin lesions. Herein, fisetin significantly ameliorated psoriasis-like disease features, and decreased the production of IL-17 by CD4+ T lymphocytes co-cultured with FTRHSP. Collectively, our data identify the prodifferentiative, antiproliferative, and anti-inflammatory effects of fisetin, via modulation of the PI3K-Akt-mTOR and p38/JNK pathways and the production of cytokines in 2D and 3D human skin models of psoriasis. These results suggest that fisetin has a great potential to be developed as an effective and inexpensive agent for the treatment of psoriasis and other related inflammatory skin disorders.

scholarly journals CD3-T Cell Receptor Co-stimulation through SLAMF3 and SLAMF6 Receptors Enhances RORγt Recruitment to theIL17APromoter in Human T Lymphocytes

2012 ◽  
Vol 287 (45) ◽  
pp. 38168-38177 ◽  
Author(s):  
Madhumouli Chatterjee ◽  
Christian M. Hedrich ◽  
Thomas Rauen ◽  
Christina Ioannidis ◽  
Cox Terhorst ◽  
...  
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Human T Lymphocytes

scholarly journals Hypoxia modulates early events in T cell receptor-mediated activation in human T lymphocytes via Kv1.3 channels

2005 ◽  
Vol 564 (1) ◽  
pp. 131-143 ◽  
Author(s):  
Jennifer R. Robbins ◽  
Susan Molleran Lee ◽  
Alexandra H. Filipovich ◽  
Peter Szigligeti ◽  
Lisa Neumeier ◽  
...  
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Human T Lymphocytes ◽  
Kv1.3 Channels

scholarly journals Transformed and Nontransformed Human T Lymphocytes Migrate to Skin in a Chimeric Human Skin/SCID Mouse Model.

1997 ◽  
Vol 109 (6) ◽  
pp. 744-750 ◽  
Author(s):  
Nathalie Rosenblatt-Velin ◽  
Jean-François Arrighi ◽  
Pierre-Yves Dietrich ◽  
Valérie Schnuriger ◽  
Isabele Masouyé ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Mouse Model ◽  
Human Skin ◽  
Scid Mouse ◽  
Human T Lymphocytes ◽  
Scid Mouse Model

scholarly journals Testing for HLA/peptide tetramer-binding to the T cell receptor complex on human T lymphocytes

2012 ◽  
Vol 2 ◽  
pp. 88-96 ◽  
Author(s):  
Pauline Weder ◽  
Ton N.M. Schumacher ◽  
Hergen Spits ◽  
Rosalie M. Luiten
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Receptor Complex ◽  
Human T Lymphocytes ◽  
Tetramer Binding

scholarly journals Human Interleukin-15 Improves Engraftment of Human T Cells in NOD-SCID Mice

2006 ◽  
Vol 13 (2) ◽  
pp. 227-234 ◽  
Author(s):  
Anyuan Sun ◽  
Haiming Wei ◽  
Rui Sun ◽  
Weihua Xiao ◽  
Yongguang Yang ◽  
...  
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
Human Lymphocytes ◽  
Scid Mice ◽  
Optimal Dosage ◽  
Dependent Manner ◽  
Human T Lymphocytes ◽  
Mouse Chimeras ◽  
T Lymphocyte Proliferation ◽  
Interleukin 15

ABSTRACT Human nonobese diabetic-severe combined immune deficiency (NOD-SCID) mouse chimeras have been widely used as an in vivo model to assess human immune function. However, only a small fraction of transferred human T lymphocytes can be detected in human peripheral blood lymphocyte (huPBL)-NOD-SCID chimeras. To improve the reconstitution of human T lymphocytes in NOD-SCID mice, the use of recombinant human interleukin-15 (rhIL-15) as a stimulator of human lymphocytes was explored. Administration of rhIL-15 after transplantation of huPBLs into NOD-SCID mice increased reconstitution of human T lymphocytes in a dose-dependent manner, with an optimal dosage of 1 μg/mouse. The number of human T lymphocytes (HLA-ABC+ CD3+) in the lymphoid organs or tissue of rhIL-15-treated huPBL-NOD-SCID mice increased 11- to 80-fold, and phytohemagglutinin-induced T-lymphocyte proliferation and cytokine production were significantly enhanced. Additionally, although mature human cells have not been thought to enter the murine thymus, human T lymphocytes were detected in the huPBL-NOD-SCID thymus after rhIL-15 treatment. Thus, rhIL-15 can be used to optimize long-term peripheral T-cell engraftment in these human-mouse chimeras and may also be useful in clinical treatment of T-cell deficiencies.

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