NK cell allorecognition shapes reprogramming of neutrophils infiltrating heart allografts.

Background: Recent developments in neutrophil biology have demonstrated that neutrophils are phenotypically and functionally heterogeneous. Tissue microenvironments dictate changes in neutrophil cell states in infection and cancer, but little is known about how alloimmune responses or solid organ transplantation influence neutrophil heterogeneity and plasticity. Methods: Here, we used the murine heterotopic heart transplant model in conjunction with high dimensional flow cytometry and transcriptome analysis to interrogate how the alloimmune response and microenvironment of a transplanted organ influence neutrophil subset differentiation and plasticity. Complete MHC mismatched A/J (H2 Results: We uncovered striking differences between neutrophils infiltrating complete MHC mismatched allografts and syngeneic isografts. Bone marrow neutrophil development was highly skewed towards an immature, interferon stimulated gene (ISG) Conclusions: These findings provide novel insights into the innate immune allorecognition-mediated regulation of the plasticity of recently described key neutrophil subsets and will enable specific targeting to neutralize detrimental neutrophil subsets and enhance solid organ transplant outcomes.