Faculty Opinions recommendation of Production of interleukin 22 but not interleukin 17 by a subset of human skin-homing memory T cells.

2009 ◽  
Author(s):  
David Woodland
Keyword(s):  
T Cells ◽  
Human Skin ◽  
Memory T Cells ◽  
Interleukin 17 ◽  
Interleukin 22 ◽  
Skin Homing

Production of interleukin 22 but not interleukin 17 by a subset of human skin-homing memory T cells

2009 ◽  
Vol 10 (8) ◽  
pp. 857-863 ◽  
Author(s):  
Thomas Duhen ◽  
Rebekka Geiger ◽  
David Jarrossay ◽  
Antonio Lanzavecchia ◽  
Federica Sallusto
Keyword(s):  
T Cells ◽  
Human Skin ◽  
Memory T Cells ◽  
Interleukin 17 ◽  
Interleukin 22 ◽  
Skin Homing

scholarly journals A novel humanized mouse model to study the function of human cutaneous memory T cells in vivo in human skin

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Maria M. Klicznik ◽  
Ariane Benedetti ◽  
Laura M. Gail ◽  
Suraj R. Varkhande ◽  
Raimund Holly ◽  
...  
Keyword(s):  
T Cells ◽  
Mouse Model ◽  
Human Skin ◽  
Memory T Cells ◽  
Humanized Mouse ◽  
Humanized Mouse Model

Neutrophils, Monocytes, and Dendritic Cells Express the Same Specialized Form of PSGL-1 as Do Skin-Homing Memory T Cells: Cutaneous Lymphocyte Antigen

2001 ◽  
Vol 285 (3) ◽  
pp. 577-587 ◽  
Author(s):  
J.David Kieffer ◽  
Robert C. Fuhlbrigge ◽  
Dieter Armerding ◽  
Caroline Robert ◽  
Katalin Ferenczi ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Memory T Cells ◽  
Lymphocyte Antigen ◽  
Skin Homing ◽  
Specialized Form ◽  
Cutaneous Lymphocyte Antigen

scholarly journals Epidermis instructs skin homing receptor expression in human T cells

Blood ◽  
2012 ◽  
Vol 120 (23) ◽  
pp. 4591-4598 ◽  
Author(s):  
Michelle L. McCully ◽  
Kristin Ladell ◽  
Svetlana Hakobyan ◽  
Robert E. Mansel ◽  
David A. Price ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Human Skin ◽  
Memory T Cells ◽  
Immune Surveillance ◽  
Receptor Expression ◽  
Epidermal Keratinocytes ◽  
Specific Factor ◽  
Peripheral Tissues ◽  
Preferential Expression

Abstract The localization of memory T cells to human skin is essential for long-term immune surveillance and the maintenance of barrier integrity. Although the mechanisms controlling memory T-cell migration to peripheral tissues are poorly understood, the current paradigm includes the localized secretion of “imprinting” signals from tissue-resident dendritic cells in the draining lymph nodes. Here we show that CCR8 expression by newly activated naive T cells is regulated by skin-specific factor(s) derived primarily from epidermal keratinocytes, thereby providing a mechanism for the preferential expression of CCR8 by skin-resident memory T cells. Importantly, no such effects were observed after coculture with primary cells from skin-unrelated epithelia, including mesothelium and small intestine. The keratinocyte-derived CCR8-inducing factor(s) were soluble, and independent of vitamins A and D. Furthermore, the induction of CCR8 under these conditions correlated with an increase in cutaneous lymphocyte-associated antigen expression. Our findings challenge current tissue homing paradigms, especially those involving CCR10, and emphasize the importance of steady-state epidermis rather than tissue-resident dendritic cells in controlling the localization of memory T cells within human skin.

Glycosylation-dependent inhibition of cutaneous lymphocyte–associated antigen expression: implications in modulating lymphocyte migration to skin

Blood ◽  
2003 ◽  
Vol 101 (2) ◽  
pp. 602-610 ◽  
Author(s):  
Charles J. Dimitroff ◽  
Ralph J. Bernacki ◽  
Robert Sackstein
Keyword(s):  
T Cells ◽  
Human Skin ◽  
Critical Role ◽  
Metabolic Inhibitors ◽  
Lymphocyte Migration ◽  
Skin Homing ◽  
Selectin Ligand ◽  
Adhesive Interactions ◽  
Selectin Binding ◽  
Ligand Activity

Constitutive E-selectin expression on dermal microvascular endothelial cells plays a critical role in mediating rolling adhesive interactions of human skin–homing T cells and in pathologic accumulation of lymphocytes in skin. The major E-selectin ligand on human skin–homing T cells is cutaneous lymphocyte–associated antigen (CLA), a specialized glycoform of P-selectin glycoprotein ligand-1 (PSGL-1) defined by monoclonal antibody HECA-452. Since HECA-452 reactivity, and not PSGL-1 polypeptide itself, confers the specificity of human T cells to enter dermal tissue, inhibition of HECA-452 expression is a potential strategy for modulating lymphocyte migration to skin. In this study, we examined the efficacy of several well-characterized metabolic inhibitors of glycosylation and of a novel fluorinated analog of N-acetylglucosamine (2-acetamido-1,3,6-tri-O-acetyl-4-deoxy-4-fluoro-D-glucopyranose [4-F-GlcNAc]) to alter HECA-452 expression on human CLA+ T cells and prevent cell tethering and rolling on selectins under shear stress. At concentrations that did not affect PSGL-1 expression, we found that swainsonine (inhibitor of complex-typeN-glycan synthesis) had no effect on HECA-452 expression or selectin ligand activity, whereas benzyl-O-N-acetylgalactosamide (BAG; inhibitor of O-glycan biosynthesis) ablated HECA-452 expression on PSGL-1 and significantly lowered selectin ligand activity. We found that 4-F-GlcNAc (putative inhibitor of poly-N-acetyllactosamine biosynthesis) was more potent than BAG at lowering HECA-452 expression and selectin binding. In addition, we show that 4-F-GlcNAc was directly incorporated into native CLA expressed on T cells, indicating direct inhibition on poly-N-acetyllactosamine elongation and selectin-binding determinants on PSGL-1 O-glycans. These observations establish a potential treatment approach for targeting pathologic lymphocyte trafficking to skin and indicate that 4-F-GlcNAc may be a promising agent for treatment of dermal tropism associated with malignancies and inflammatory disorders.

scholarly journals A novel humanized mouse model to study the function of human cutaneous memory T cells in vivo in human skin

2018 ◽  
Author(s):  
Maria M. Klicznik ◽  
Ariane Benedetti ◽  
Laura M. Gail ◽  
Suraj R. Varkhande ◽  
Raimund Holly ◽  
...  
Keyword(s):  
T Cells ◽  
Candida Albicans ◽  
T Cell ◽  
Human Skin ◽  
Skin Diseases ◽  
Memory T Cells ◽  
Human Memory ◽  
Human Pbmc ◽  
Human T Cell

AbstractHuman skin contains a population of memory T cells that support tissue homeostasis and provide protective immunity. The study of human memory T cells is often restricted to in vitro studies and to human PBMC serving as primary cell source. Because the tisse environment impacts the phenotype and function of memory T cells, it is crucial to study these cells within their tissue. Here we utilized immunodeficient NOD-scid IL2rγnull (NSG) mice that carried in vivo-generated engineered human skin (ES). ES were generated from human keratinocytes and fibroblasts and is initially devoid of skin-resident immune cells. Upon adoptive transfer of human PBMC this reductionist system allowed to study human T cell recruitment from a circulating pool of T cells into non-inflamed human skin in vivo. Circulating human memory T cells preferentially infiltrated ES and showed diverse functional profiles of T cells found in fresh human skin. The chemokine and cytokine microenvironment of ES closely resembled that of non-inflamed human skin. Upon entering the ES T cells assumed a resident memory T cell-like phenotype in the absence of infection, and a proportion of these cutaneous T cells can be locally activated upon injection of monocyte derived dendritic cells (moDCs) that presented Candida albicans. Interestingly, we found that CD69+ memory T cells produced higher levels of effector cytokines in response to Candida albicans, compared to CD69- T cells. Overall, this model has broad utility in many areas of human skin immunology research, including the study of immune-mediated skin diseases.

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