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

Abstract

Innate lymphoid cells (ILC) 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 characterise the ILC 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 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 blood of psoriasis patients compared to 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 ILC in skin compared to blood. Moreover the frequency of NKp44+ ILC3 was significantly increased in non-lesional psoriatic skin compared to normal skin. A detailed time course of a psoriasis patient treated with anti-TNF 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.

Functional and phenotypic heterogeneity of group 3 innate lymphoid cells

“…IL‐17A production by CCR6 + ILC3 is required for Klebsiella pneumoniae clearance and contributes to protection against systemic Candida albicans infection 53, 123. ILC3‐derived IL‐17A has further been associated with pathogenesis of obesity‐associated airway inflammation and psoriasis in mice and humans 124, 125, 126. Although relatively less characterized, ILC3 also secrete IL‐17F and a role for this cytokine in skin inflammation has also been suggested 127…”

Interleukin‐17‐producing γδ T (γδ17) cells in inflammatory diseases

“…In this report, however, V γ 9 + V δ 2 + cells were activated to produce cytokines from keratinocytes by the specific antigen, suggesting that recognition of specific antigens may be important for the development of psoriasis. Because Th17 cells94 and ILC3s95 as well as γδ 17 cells91 are also detected in the psoriatic skin, the involvement of autoimmunity and the main source of IL‐17 during the development of psoriasis still remain obscure in humans.…”

Emerging roles of innate lymphoid cells in inflammatory diseases: Clinical implications

“…81 The numbers of IL-22-producing ILC3s were increased in both lesional and nonlesional skin ( Figure 2) and blood of patients with psoriasis, compared to healthy subjects. 12,82,83 Additionally, the increased ILC3 numbers in skin lesions correlated with psoriasis severity 12 and ILC3s produced IL-22 in response to stimulation with IL-1b and IL-23. IL-22 may limit the ongoing inflammation, paralleling its role in epithelial maintenance in the gut.…”