Editors' ChoiceHEMATOLOGY

More than just a platelet factory

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Science Translational Medicine  04 Nov 2020:
Vol. 12, Issue 568, eabf2646
DOI: 10.1126/scitranslmed.abf2646


Megakaryocytes are found in the lungs of mice and nonhuman primates, where they have a tissue-dependent antigen-presenting cell role and can activate CD4+ T cells.

The role of platelets and their precursors, megakaryocytes, has long been thought to be restricted to hemostasis. More recently, platelets have been found to have a plethora of important immune functions, including the regulation of T cell activation and differentiation; these effects are in part mediated by the ability of megakaryocytes and platelets to cross-present antigen on major histocompatibility complex (MHC) class I molecules. Megakaryocytes are predominantly found in the bone marrow but have been found in other organs in both mice and humans, including the lungs. Recent transcriptional data in mice suggest that lung megakaryocytes may have a substantially greater immunologic function than bone marrow megakaryocytes.

Pariser and colleagues recently sought to characterize the immunologic role of lung megakaryocytes in mice and macaques. The authors confirmed that lung megakaryocytes were transcriptionally distinct from bone marrow megakaryocytes. In mice, lung megakaryocytes had a transcriptional profile that more closely aligned with dendritic cells; in both mice and macaques, lung megakaryocytes expressed much higher levels of MHC class II and costimulatory molecules than did bone marrow megakaryocytes. Interestingly, this antigen presenting cell phenotype in mice was inducible in bone marrow megakaryocytes in vitro under inflammatory conditions and in vivo upon relocation to the lungs; thus, megakaryocytes appeared to maintain plasticity in their phenotype and function but were affected by the immunologic milieu of the organ in which they resided. Murine lung megakaryocytes appeared superior to bone marrow megakaryocytes in their ability to phagocytose, process, and present antigen. Murine lung megakaryocytes could promote inflammatory reactions to Escherichia coli pathogen challenges in vivo and activate CD4+ T cells in vitro and in vivo in an MHC class II–dependent manner.

Overall, this work ascribes an important and previously unappreciated immunologic role of antigen presenting cell to lung megakaryocytes. Further study is required to determine the relative contribution of lung megakaryocytes and other antigen-presenting cells like dendritic cells to pathologic conditions, whether immune responses can be shaped by modulating the function of these lung megakaryocytes, and to what extent these findings are conserved in humans. Moreover, whether megakaryocytes found in other organs may serve similar immune functions is unknown. Ultimately, this work prompts future study to delineate the potential role that lung megakaryocytes may play in shaping immune responses to infectious or inflammatory pulmonary conditions including pneumonia, asthma, allergic responses, or lung transplantation.

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