Rapid, Treatment-Sensitive Graft Infiltration By Novel Lineage Negative RORγt⁺ Hematopoietic Cells

Using in vivo imaging and cell phenotype monitoring, we identified a previously uncharacterized Lineage-RORγt⁺ early hematopoietic cell population with multi-lineage potential infiltrating allograft, syngeneic and sham transplant sites. They are distinctly different from Th17 cells, TCR γδ T, and iNKT cells. Some Lineage-RORγt⁺ infiltrating cells are CD127⁺ or NKp46⁺, and therefore, are likely group 3 innate lymphoid cells (ILC3s). ILC3 are known to have a powerful effect on the conduct of inflammation. Additionally, some of these Lineage-RORgt⁺ cells express classical hematopoietic stem cells traits "LSK" (Lineage-Sca-1⁺c-kit⁺). The genetic ablation of RORγt expression and treatment with alpha1 anti-trypsin (AAT), a treatment that reduces inflammation, also reduces infiltration by RORγt⁺ cells at the graft site. Taken together, these data suggest an important role for RORγt⁺ cells in the allograft response.

Jiafan Liu and Zhenni Zhao are the co-first author for the abstract