Psoriasis is thought to be predominantly driven by both CD4+ and CD8+ of the Th17/Tc17 lineages, with an established key role for the Th17 cytokine network, including IL-17 and IL-22. Here, we have explored the possibility that a dysregulation of group 3 innate lymphoid cells (ILC3s)  may also be involved in psoriasis pathobiology, by using a modification of our well-established human skin xenotransplant mouse model. 
Autologous peripheral blood human ILC3s were purified from PBMCs and intradermally injected into normal human skin grafts of healthy donors. Positive control groups were composed of peripheral autologous Th17 and IL-2 enriched PBMCs.  Induction of psoriatic lesions is observed after transfer of autologous IL-2 enriched PBMCs into normal human skin on SCID mice. Negative control group was composed of culture cells without the presence of ILC3 and TH17 and thus contained cultured cells without the expression of CD3, NKp44 and RORγt markers. Flow cytometric analysis revealed intracellular expression of these cytokines in the cultured ILC3s of the healthy population, Flow cytometric analysis revealed intracellular expression of these cytokines in the cultured ILC3s of the healthy population, indicating the activity of the cells. Injections of autologous ILC3s induced the development of psoriatic–like phenotype in the normal human skin grafts. In order to ensure that dermal resident cells or residual CD3+ cell within the purified ILC3s were not involved in psoriasis induction, a group of grafted mice were sub-lethally irradiated prior to the injection of cultured cells or treated daily with anti-CD3+ cells (OKT3) antibodies for 30 days just after the cell injections. This demonstrated that neither irradiation nor injections of anti CD3+ antibodies prevented the induction of the psoriatic lesions in human skin xenotransplants in vivo by autologous ILC3s. Hence, our study is the first to strongly implicated ILC3s early psoriasis pathobiology.

Group 3 innate lymphoid cells (ILC3) induce psoriasiform lesions in human skin xenotransplants in vivo