Innate lymphoid cells (ILCs) are increasingly appreciated as important regulators of tissue homeostasis and inflammation. However, their role in human skin remains obscure. We found that healthy peripheral blood CD117(+) ILC3, lacking the natural cytotoxicity receptor (NCR) NKp44 (NCR(-) ILC3), CD117(-)NCR(-)CRTH2(-)CD161(+) ILC1, and CRTH2(+) ILC2, express the skin-homing receptor cutaneous lymphocyte antigen (CLA). NCR(+) ILC3 were scarce in peripheral blood. Consistently, we identified in normal skin ILC2 and NCR(-) ILC3, a small proportion of CD161(+) ILC1, and hardly any NCR(+) ILC3, whereas NCR(+) ILC3 were present in cultured dermal explants. The skin ILC2 and NCR(+) ILC3 subsets produced IL-13 and IL-22, respectively, upon cytokine stimulation. Remarkably, dermal NCR(-) ILC3 converted to NCR(+) ILC3 upon culture in IL-1β plus IL-23, cytokines known to be involved in psoriatic inflammation. In line with this observation, significantly increased proportions of NCR(+) ILC3 were present in lesional skin and peripheral blood of psoriasis patients as compared with skin and blood of healthy individuals, respectively, whereas the proportions of ILC2 and CD161(+) ILC1 remained unchanged. NCR(+) ILC3 from skin and blood of psoriasis patients produced IL-22, which is regarded as a key driver of epidermal thickening, suggesting that NCR(+) ILC3 may participate in psoriasis pathology.

Phototherapy can be a valid therapeutic option for patients with AD. Based on the results of this review, preference is given to UVA1 and NB-UVB. Further well-designed, adequately powered RCTs are required.

Based on this relatively small pragmatic study, MTX and AZA seem to be effective and safe as maintenance treatments in moderate-to-severe AD up to 5 years. Few patients in both groups survive on their originally allocated drug although some discontinued because of controlled AD.

Long-term data of methotrexate (MTX) and azathioprine (AZA) in atopic dermatitis (AD) are lacking. Previously, we published the results of a randomized controlled trial of 42 adults with severe AD treated with MTX or AZA for 12 to 24 weeks. Both MTX and AZA induced significant reductions in SCORing Atopic Dermatitis (SCORAD) index at 12 and 24 weeks after baseline, without a significant difference between treatments. 1 To assess long-term efficacy and safety of MTX versus AZA, all 42 patients were asked to participate in an observational follow-up study to be evaluated 3 monthly for 2 years. After 12 weeks of treatment with MTX or AZA, treatments were continued, stopped, or switched, reflecting normal clinical practice. The same outcomes as in the original randomized controlled trial were investigated, which correspond to the 4 core outcome domains for AD suggested by the Harmonising Outcome Measures for Eczema initiative. Patients were scored by trained blinded investigators. One of the primary outcomes was the difference in mean absolute and relative change in SCORAD