Immune and Inflammatory Properties of Megakaryocytes

Abstract

Megakaryocytes (MKs), which primarily develop in bone marrow (BM) from hematopoietic stem cells, are critical for platelet production. Beyond their well-established role in thrombopoiesis, MKs have been identified as important for BM niche maintenance, such as by supporting the growth and differentiation of other cell types. Recently, megakaryopoiesis has been reported as yielding divergent subpopulations of MKs, as evidenced by single-cell RNA sequencing of lung, spleen, or BM resident MKs. Interestingly, these subpopulations constitute a significant proportion of "immune MKs" expressing various classical immune markers and capable of phagocytosing pathogens and contributing to antigen presentation. As such, MKs were also found to regulate inflammation, mainly by secreting various cytokines and chemokines to crosstalk with other cell types. The level and functional signature of these "immune MKs" were found to be altered in various pathological conditions, indicative of their purposeful values in health and diseases. In this review, we survey and highlight newly reported functional immune and inflammatory properties of MKs in health and in select pathologies.

Keywords: bone marrow; hematopoiesis; immune megakaryocytes; megakaryocytes; platelets.

Figure 1

Organ specific megakaryocyte (MK) residents and function. (A) MKs participate in maintaining a bone marrow (BM) niche by supporting the growth and differentiation of other cells, including stroma and fibroblasts. MK-derived CXCL4 and TGF-β contribute to maintaining HSC quiescence, whereas FGF1, in response to myeloablative stress, enhances HSC proliferation in BM. (B) Additionally, a phenotypic hematopoietic stem cell (HSC) compartment is also reported to have stem-like MK-committed progenitors (SL-MkPs), as a lineage-restricted emergency pool for megakaryopoiesis, especially during inflammatory insults. (C) Intravascular (circulatory) lung MKs are reported to produce platelets, which enter the circulation, while extravascular MKs (MK_Ls) are smaller with a typical immune signature. (D) MK_Ls are reported to act as antigen-presenting cells (APCs) and activate CD4+ T cells, thus contributing to pathogen recognition and immune responses. (E) Spleen harboring immune-skewed MKs were found to produce CD40 ligand^High-platelets, which also have immunomodulatory functions.