*Purpose: Determine whether human innate lymphoid cells (ILCs) can be isolated, expanded and used in cell-based therapies to prevent Graft-versus Host Disease (GvHD) .

*Methods: ILC2s and ILC3s are isolated from human blood and deceased donor spleen using fluorescence activated cell sorting. These ILCs are expanded in vitro using cytokines known to activate these ILC populations. After expansion, flow cytometry is used to phenotype the cells and cytometric bead arrays are used to determine the cytokine production. The impact these ILCs have on T cell activation or function is tested being co-culturing ILCs with T cells. Expanded ILCs are also infused into a xenograft model of acute GvHD in NSG mice to determine whether the ILCs can suppress xenograft GvHD symptoms and improve xenograft GvHD survival.

*Results: ILC2s and ILC3s expanded using this approach maintain expression of their signature cytokines and transcription factors. They also produce high levels of the regulatory cytokine IL-10 and the tissue repair factor amphiregulin. In xenograft GvHD studies, infusion of expanded ILC2s or ILC3s prolonged the survival of the mice and reduce xenograft GvHD severity. In vitro studies demonstrated expanded ILC2s and ILC3s can directly regulate allogenic T cells.

*Conclusions: These studies support the potential of ILC2s and ILC3s in cell-based therapies aimed at preventing the development of GvHD following hematopoietic stem cell transplant.

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