Innate lymphoid cells 3 induce psoriasis in xenotransplanted healthy human skin

To the Editor: Recent studies have demonstrated that the number of group 3 innate lymphoid cells (ILC3s) is increased in peripheral blood, lesional skin, and nonlesional skin of patients with psoriasis.1,E1,E2 However, definitive evidence is as yet entirely missing that these innate immunocytes, which produce IL-22 and IL-17, but not TNF-α or IFN-γ, and lack cytotoxic effectors,E2 are functionally involved in the induction of psoriatic lesions in human skin. [...]the present study aimed to determine whether human ILC3s (ie, CD3− RORγt+ NKp44+ cells)E1 suffice to induce psoriatic lesions in healthy human skin in vivo. Flow cytometric analysis documented the absence of γδ T cells and natural killer (NK) cells in the ILC3 preparation, while 5% γδ T cells and NK cells were present in the TH17/Tc17 cell cultures (Fig E2, D).6 The purified ILC3s were associated with the expected intracellular cytokine expression pattern5,7,E9: 78% of ILC3s showed IL-22 expression, and 10% ± 3% of these cells were double-positive for both IL-17 and IL-22 (Fig E3, B). Animal handling was in accordance with the national guidelines and approved by the Technion Animal Care and Use Committee.Culture of cells with IL2 and AhR agonist To obtain an enriched RORγt + cell culture, PBMCs from 8 normal volunteers were incubated with a high dose of IL-2 (100 U/mL) and AhR agonistE12,E13 200 nM (6-formylindolo carbazole, Enzo) for 14 days.E7Magnetic isolation of TH17-cell and ILC subsets from IL2+AhR-activated PBMC cultures Separation was performed using anti-CD3 antibodies conjugated to ferromagnetic microbeads (Miltenyi Biotec, Bergisch Gladbach, Germany) and directed through a cell separation column containing a magnetic field (Miltenyi Biotec).