Lung megakaryocytes are immune modulatory cells

Although platelets are the cellular mediators of thrombosis, they are also immune cells. Platelets interact both directly and indirectly with immune cells, impacting their activation and differentiation, as well as all phases of the immune response. Megalcaryocytes (Mks) are the cell source of circulating platelets, and until recently Mks were typically only considered bone marrow-resident (BM-resident) cells. However, platelet-producing Mks also reside in the lung, and lung Mks express greater levels of immune molecules compared with BM Mks. We therefore sought to define the immune functions of lung Mks. Using single-cell RNA sequencing of BM and lung myeloid-enriched cells, we found that lung Mks, which we term Mk(L), had gene expression patterns that are similar to antigen-presenting cells. This was confirmed using imaging and conventional flow cytometry. The immune phenotype of Mks was plastic and driven by the tissue immune environment, as evidenced by BM Mks having an Mk(L)-like phenotype under the influence of pathogen receptor challenge and lung-associated immune molecules, such as IL-33. Our in vitro and in vivo assays demonstrated that Mk(L) internalized and processed both antigenic proteins and bacterial pathogens. Furthermore, Mk(L) induced CD4(+) T cell activation in an MHC II-dependent manner both in vitro and in vivo. These data indicated that Mk(L) had key immune regulatory roles dictated in part by the tissue environment.

Automated summary

Platelets, previously known as cellular mediators of thrombosis, are also immune cells that interact with immune cells, impacting their activation and differentiation. Lung megakaryocytes (Mk(L)) have gene expression patterns similar to antigen-presenting cells, and have key immune regulatory roles influenced by the tissue environment. This indicates the plasticity of the immune phenotype of Mk(L) and their ability to induce T cell activation.