Lung megakaryocytes are immune modulatory cells
Daphne N. Pariser, … , James Palis, Craig N. Morrell
Daphne N. Pariser, … , James Palis, Craig N. Morrell
Published October 20, 2020
Citation Information: J Clin Invest. 2021;131(1):e137377. https://doi.org/10.1172/JCI137377.
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Research Article Hematology Inflammation

Lung megakaryocytes are immune modulatory cells

Abstract

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. Megakaryocytes (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 MkL, 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 MkL-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 MkL internalized and processed both antigenic proteins and bacterial pathogens. Furthermore, MkL induced CD4+ T cell activation in an MHC II–dependent manner both in vitro and in vivo. These data indicated that MkL had key immune regulatory roles dictated in part by the tissue environment.

Authors

Daphne N. Pariser, Zachary T. Hilt, Sara K. Ture, Sara K. Blick-Nitko, Mark R. Looney, Simon J. Cleary, Estheany Roman-Pagan, Jerry Saunders II, Steve N. Georas, Janelle Veazey, Ferralita Madere, Laura Tesoro Santos, Allison Arne, Nguyen P.T. Huynh, Alison C. Livada, Selena M. Guerrero-Martin, Claire Lyons, Kelly A. Metcalf-Pate, Kathleen E. McGrath, James Palis, Craig N. Morrell

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Figure 6

Lung Mks process and present antigen in vivo.

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Lung Mks process and present antigen in vivo. (A) Mice were treated with...
(A) Mice were treated with control buffer or DQ-Ova via the o.p. route. Eighty minutes later real-time in vivo lung imaging was performed (representative image). (B) Twenty-four hours later DQ-Ova lungs were also isolated to quantify fluorescent Mks. Lung Mks internalized antigen (unpaired t test). (C and D) Lung Mks are more phagocytic than BM Mks. BM and lung Mks were incubated with control buffer or GFP E. coli and 30 minutes later fluorescence was determined by (C) ImageStream (representative images) and (D) bacteria internalization was quantified (unpaired t test). BF, bright field. (E) Lung Mks take up E. coli in vivo. E. coli was delivered via the o.p. route and 3 hours later E. coli–positive lung Mks and DCs were quantified by flow cytometry (unpaired t test). *P = 0.01 to 0.05; ***P = 0.0001 to 0.001; ****P < 0.0001.