Characterization of Innate Lymphoid Cells in Human Skin and Blood Demonstrates Increase of NKp44+ILC3 in Psoriasis

TY - JOUR

T1 - Characterization of Innate Lymphoid Cells in Human Skin and Blood Demonstrates Increase of NKp44+ILC3 in Psoriasis

AU - Villanova, Federica

AU - Flutter, Barry

AU - Tosi, Isabella

AU - Grys, Katarzyna

AU - Sreeneebus, Hemawtee

AU - Perera, Gayathri

AU - Chapman, Anna

AU - Smith, Catherine

AU - Di Meglio, Paola

AU - Nestle, Frank

PY - 2014/4/1

Y1 - 2014/4/1

N2 - Innate lymphoid cells (ILCs) are increasingly appreciated as key regulators of tissue immunity. However, their role in human tissue homeostasis and disease remains to be fully elucidated. Here we characterize the ILCs in human skin from healthy individuals and from the inflammatory skin disease psoriasis. We show that a substantial proportion of IL-17A and IL-22 producing cells in the skin and blood of normal individuals and psoriasis patients are CD3-negative innate lymphocytes. Deep immunophenotyping of human ILC subsets showed a statistically significant increase in the frequency of circulating NKp44+ ILC3 in the blood of psoriasis patients compared with healthy individuals or atopic dermatitis patients. More than 50% of circulating NKp44+ ILC3 expressed cutaneous lymphocyte–associated antigen, indicating their potential for skin homing. Analysis of skin tissue revealed a significantly increased frequency of total ILCs in the skin compared with blood. Moreover, the frequency of NKp44+ ILC3 was significantly increased in non-lesional psoriatic skin compared with normal skin. A detailed time course of a psoriasis patient treated with anti–tumor necrosis factor showed a close association between therapeutic response, decrease in inflammatory skin lesions, and decrease of circulating NKp44+ ILC3. Overall, data from this initial observational study suggest a potential role for NKp44+ ILC3 in psoriasis pathogenesis.

AB - Innate lymphoid cells (ILCs) are increasingly appreciated as key regulators of tissue immunity. However, their role in human tissue homeostasis and disease remains to be fully elucidated. Here we characterize the ILCs in human skin from healthy individuals and from the inflammatory skin disease psoriasis. We show that a substantial proportion of IL-17A and IL-22 producing cells in the skin and blood of normal individuals and psoriasis patients are CD3-negative innate lymphocytes. Deep immunophenotyping of human ILC subsets showed a statistically significant increase in the frequency of circulating NKp44+ ILC3 in the blood of psoriasis patients compared with healthy individuals or atopic dermatitis patients. More than 50% of circulating NKp44+ ILC3 expressed cutaneous lymphocyte–associated antigen, indicating their potential for skin homing. Analysis of skin tissue revealed a significantly increased frequency of total ILCs in the skin compared with blood. Moreover, the frequency of NKp44+ ILC3 was significantly increased in non-lesional psoriatic skin compared with normal skin. A detailed time course of a psoriasis patient treated with anti–tumor necrosis factor showed a close association between therapeutic response, decrease in inflammatory skin lesions, and decrease of circulating NKp44+ ILC3. Overall, data from this initial observational study suggest a potential role for NKp44+ ILC3 in psoriasis pathogenesis.

KW - RESIDENT T-CELLS

KW - IMMUNITY

KW - TISSUE

KW - IDENTIFICATION

KW - MECHANISMS

KW - INFECTION

KW - DISEASE

KW - IL-22

KW - GAMMA

KW - IL-17

U2 - 10.1038/jid.2013.477

DO - 10.1038/jid.2013.477

M3 - Article

SN - 0022-202X

VL - 134

SP - 984

EP - 991

JO - Journal of Investigative Dermatology

JF - Journal of Investigative Dermatology

IS - 4

ER -