Laser‐assisted epicutaneous immunization to target human skin dendritic cells

Macrophage tropic HIV-1 is predominant during the initial viremia after person to person transmission of HIV-1 (Zhu, T., H. Mo, N. Wang, D.S. Nam, Y. Cao, R.A. Koup, and D.D. Ho. 1993. Science. 261:1179–1181.), and this selection may occur during virus entry and carriage to the lymphoid tissue. Human skin explants were used to model HIV-1 selection that may occur at the skin or mucosal surface. Macrophage tropic, but not T cell line tropic strains of HIV-1 applied to the abraded epidermis were recovered from the cells emigrating from the skin explants. Dermis and epidermis were separated by dispase digestion after virus exposure to determine the site of viral selection within the skin. Uptake and transmission to T cells of all HIV-1 isolates was found with the dermal emigrant cells, but only macrophage tropic virus was transferred by emigrants from the epidermis exposed to HIV-1, indicating selection only within the epidermis. CD3+, CD4+ T cells were found in both the dermal and epidermal emigrant cells. After cell sorting to exclude contaminating T cells, macrophage tropic HIV-1 was found in both the dermal emigrant dendritic cells and in dendritic cells sorted from the epidermal emigrants. These observations suggest that selective infection of the immature epidermal dendritic cells represents the cellular mechanism that limits the initial viremia to HIV-1 that can use the CCR5 coreceptor.

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Construction of Three-dimensional Human Skin Model Involving Dendritic Cells and Its Application to Skin Sensitization Test

YAKUGAKU ZASSHI ◽

10.1248/yakushi.128.45 ◽

2008 ◽

Vol 128 (1) ◽

pp. 45-50 ◽

Cited By ~ 8

Author(s):

Tadashi UCHINO ◽

Toshiaki TAKEZAWA ◽

Yoshiaki IKARASHI ◽

Hiroshi TOKUNAGA

Keyword(s):

Dendritic Cells ◽

Human Skin ◽

Three Dimensional ◽

Skin Sensitization ◽

Skin Model

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Prolonged Maturation and Enhanced Transduction of Dendritic Cells Migrated from Human Skin Explants After In Situ Delivery of CD40-Targeted Adenoviral Vectors

The Journal of Immunology ◽

10.4049/jimmunol.169.9.5322 ◽

2002 ◽

Vol 169 (9) ◽

pp. 5322-5331 ◽

Cited By ~ 53

Author(s):

Tanja D. de Gruijl ◽

Sylvia A. Luykx-de Bakker ◽

Bryan W. Tillman ◽

Alfons J. M. van den Eertwegh ◽

Jan Buter ◽

...

Keyword(s):

Dendritic Cells ◽

Human Skin ◽

Adenoviral Vectors ◽

Skin Explants

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Epidermis instructs skin homing receptor expression in human T cells

Blood ◽

10.1182/blood-2012-05-433037 ◽

2012 ◽

Vol 120 (23) ◽

pp. 4591-4598 ◽

Cited By ~ 56

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.

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O06.2 Initial interactions of herpes simplex virus with human skin dendritic cells

10.1136/sextrans-2017-053264.31 ◽

2017 ◽

Author(s):

Cunningham AL ◽

M Kim ◽

Truong NR ◽

Sandgren KJ ◽

Harman AN ◽

...

Keyword(s):

Dendritic Cells ◽

Herpes Simplex Virus ◽

Herpes Simplex ◽

Human Skin ◽

Simplex Virus

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CD4+ T Cell Responses Elicited by Different Subsets of Human Skin Migratory Dendritic Cells

The Journal of Immunology ◽

10.4049/jimmunol.175.12.7905 ◽

2005 ◽

Vol 175 (12) ◽

pp. 7905-7915 ◽

Cited By ~ 81

Author(s):

Adrian E. Morelli ◽

J. Peter Rubin ◽

Geza Erdos ◽

Olga A. Tkacheva ◽

Alicia R. Mathers ◽

...

Keyword(s):

Dendritic Cells ◽

T Cell ◽

Human Skin ◽

T Cell Responses ◽

Cd4 T Cell ◽

Cell Responses

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Poised cell circuits in human skin are activated in disease

10.1101/2020.11.05.369363 ◽

2020 ◽

Author(s):

Gary Reynolds ◽

Peter Vegh ◽

James Fletcher ◽

Elizabeth F.M. Poyner ◽

Emily Stephenson ◽

...

Keyword(s):

Dendritic Cells ◽

Human Skin ◽

Immune Cell ◽

Vascular Endothelial Cells ◽

Single Cells ◽

Lymphoid Cells ◽

Keratinocyte Differentiation ◽

Cell Trafficking ◽

Immunological Protection ◽

Cellular Circuits

AbstractThe human skin confers biophysical and immunological protection through a complex cellular network that is established early in development. We profiled ~500,000 single cells using RNA-sequencing from healthy adult and developing skin, and skin from patients with atopic dermatitis and psoriasis. Our findings reveal a predominance of innate lymphoid cells and macrophages in developing skin in contrast to T cells and migratory dendritic cells in adult skin. We demonstrate dual keratinocyte differentiation trajectories and activated cellular circuits comprising vascular endothelial cells mediating immune cell trafficking, disease-specific clonally expanded IL13/IL22 and IL17A/F-expressing lymphocytes, epidermal IL23-expressing dendritic cells and inflammatory keratinocytes in disease. Our findings provide key insights into the dynamic cellular landscape of human skin in health and disease.One Sentence SummarySingle cell atlas of human skin reveals cell circuits which are quantitatively and qualitatively reconfigured in inflammatory skin disease.

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