A simple and efficient method for the robust expansion of human ILC2s to prevent acute GVHD.

Abstract

Reconstitution of stem cells and enhancement of the barrier function of the gastrointestinal (GI) tract is critical to the resolution of intestinal acute graft-versus-host disease (aGVHD). Previously, our group has shown in murine models that type 2 innate lymphoid cells (ILC2s) generate proteins in the GI tract that enhanced GI tract barrier function, and diminished the expansion and function of proinflammatory donor cells when given to recipients of allogeneic stem cell transplant. Therefore, the infusion of donor ILC2s could treat or prevent GI tract aGVHD but, for this approach to be clinically applicable, robust expansion of a homogeneous population of human ILC2s is needed. Here, we describe a method for the rapid expansion of a uniform population of human ILC2s that decrease GVHD in NOD scid gamma mice. The addition of interleukin 4 to the culture was critical to prevent the expansion of proinflammatory ILC1-like cells. Our approach should allow for the evaluation of human ILC2 cells to treat therapy-resistant GI tract aGVHD.