Innate lymphoid cells in allogenic hematopoietic cell transplantation

Allogeneic hematopoietic cell transplantation (HCT) is often complicated by graft versus host disease (GvHD), an alloreactive immune response triggered by tissue damage. Interleukin (IL)-22 producing type 3 innate lymphoid cells (ILC3) protect epithelial tissues against chemo(radio)therapy-induced damage, suppress alloreactive T cells and mitigate acute GvHD symptoms after allogeneic HCT. We demonstrated that patients with acute GvHD of the skin had significantly lower proportions of ILC in the skin than healthy individuals. In addition, mesenchymal stromal cells (MSC) enhance the proliferation and IL-22 production of ILC3. To generate ILC, we set up a protocol and found that the capacity of hematopoietic progenitor cells (HPC) to develop into ILC varied depending on the HPC source. HPC from fetal and neonatal sources developed more readily into ILC compared to HPC from adult sources. Another factor important for ILC reconstitution and ILC function after allogeneic HCT is the effect of immunosuppressants that are known to suppress T cell function and proliferation, did not have the same suppressive effect on ILC3 proliferation and cytokine production. The drug exporter expression levels of functionally active ATP Binding Cassette Subfamily B Membrane 1 (ABCB1) drug exporter proteins were higher on ILC compared to T cells. Together, our findings underline the importance of ILC in GvHD pathophysiology, and we uncovered factors that are important in recovery of the ILC population after allogeneic HCT. These findings could be useful in the development of therapeutic strategies to prevent and treat GvHD.