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Poised cell circuits in human skin are activated in disease

by Reynolds, Gary , Huang, Ni , Lisgo, Steven , Edel A O’toole , Hagai, Tzachi , Behjati, Sam , Jones, Phil , Goh, Issac , Vegh, Peter , Jong-Eun Park , Dubois, Anna , Husain, Akhtar , Poyner, Elizabeth Fm , Botting, Rachel A , Bacardit, Jaume , Xiao-Nong Wang , Engelbert, Justin , Carey, Christopher , Horsfall, Dave , Rajan, Neil , Sayer, Ben , Jones, Claire , Maunder, Daniel , Filby, Andrew , Mcdonald, David , Vento-Tormo, Roser , Lynch, Magnus , Watt, Fiona , Fletcher, James , Reynolds, Nick J , Mcgrath, Jim , Teichmann, Sarah A , Ness, Thomas , Belokhvostova, Daria , Haniffa, Muzlifah , Coxhead, Jonathan , Negri, Victor A , Popescu, Dorin-Mirel , Villani, Alexandra-Chloé , Olabi, Bayanne , Green, Kile , Webb, Simone , Efremova, Mirjana , Ogg, Graham S , Meyer, Kerstin B , Polański, Krzysztof , Stephenson, Emily , Dixon, David , Jardine, Laura

in Atopic dermatitis / Cell migration / Circuits / Dendritic cells / Endothelial cells / Immunology / Interleukin 1 / Interleukin 13 / Interleukin 22 / Interleukin 23 / Keratinocytes / Lymphocytes T / Lymphoid cells / Macrophages / Psoriasis / Skin diseases

2020

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2020

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2020

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Paper

Poised cell circuits in human skin are activated in disease

Reynolds, Gary,

Huang, Ni,

Lisgo, Steven,

Edel A O’toole,

Hagai, Tzachi,

Behjati, Sam,

Jones, Phil,

Goh, Issac,

Vegh, Peter,

Jong-Eun Park,

Dubois, Anna,

Husain, Akhtar,

Poyner, Elizabeth Fm,

Botting, Rachel A,

Bacardit, Jaume,

Xiao-Nong Wang,

Engelbert, Justin,

Carey, Christopher,

Horsfall, Dave,

Rajan, Neil,

Sayer, Ben,

Jones, Claire,

Maunder, Daniel,

Filby, Andrew,

Mcdonald, David,

Vento-Tormo, Roser,

Lynch, Magnus,

Watt, Fiona,

Fletcher, James,

Reynolds, Nick J,

Mcgrath, Jim,

Teichmann, Sarah A,

Ness, Thomas,

Belokhvostova, Daria,

Haniffa, Muzlifah,

Coxhead, Jonathan,

Negri, Victor A,

Popescu, Dorin-Mirel,

Villani, Alexandra-Chloé,

Olabi, Bayanne,

Green, Kile,

Webb, Simone,

Efremova, Mirjana,

Ogg, Graham S,

Meyer, Kerstin B,

Polański, Krzysztof,

Stephenson, Emily,

Dixon, David,

Jardine, Laura

2020

Overview

Abstract The 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 Summary Single cell atlas of human skin reveals cell circuits which are quantitatively and qualitatively reconfigured in inflammatory skin disease. Competing Interest Statement The authors have declared no competing interest.

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Cold Spring Harbor Laboratory Press,Cold Spring Harbor Laboratory

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