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• Correspondence on “Rheumatoid arthritis, systemic lupus erythematosus and primary Sjogren's syndrome shared megakaryocyte expansion in peripheral blood” by Wang, Y. et al
  Hui Wu, Hongxing Wang and Yi Zhang
  Published on: 14 February 2022

• Published on: 14 February 2022

  Correspondence on “Rheumatoid arthritis, systemic lupus erythematosus and primary Sjogren's syndrome shared megakaryocyte expansion in peripheral blood” by Wang, Y. et al

  • Hui Wu, PhD The Eighth Affiliated Hospital of Sun Yat-sen University
  • Other Contributors:
    • Hongxing Wang, PhD
    • Yi Zhang, Professor

  With great interest, we read the article by Wang Y et al., which suggested that Megakaryocytes (MKs) expansion might contribute to the pathogenesis of Rheumatoid Arthritis (RA)1. MKs are large, polyploid cells that originate from hematopoietic stem cells (HSC) and give rise to platelets. However, the authors fall short in recognizing the role of MK-derived platelets in RA.
  Wang Y et al. identified increased MKs in peripheral blood of RA using single-cell RNA sequencing and flow cytometry approaches. They provide clues that MKs act as specific endogenous antigen-presenting cells (APCs), triggering the initial autoimmune T cell for RA pathogenesis1. Of note, novel evidence suggests that MKs derived from bone marrow (BM), lung2 and liver3, instead serve as immunomodulatory or secretory cells4. The generation of platelets is the primary function of MKs.
  Indeed, many characteristics and roles of platelets inherit from MKs. For example, once activated, platelets present antigens via MHC class I molecules (MHC-I) derived from parent MKs5; in this way, the immunogenic information can be conveyed to platelets. Similarly, platelets can also act as an essential immune effector in RA6. An array of platelet surface receptors is responsible for activation, adhesion, and thrombus formation via initiating a complex network of signaling pathways in the presence of ligands. In addition, it is well known that ligands for platelet receptors such as collagen, fibrinogen, serotonin,...

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  With great interest, we read the article by Wang Y et al., which suggested that Megakaryocytes (MKs) expansion might contribute to the pathogenesis of Rheumatoid Arthritis (RA)1. MKs are large, polyploid cells that originate from hematopoietic stem cells (HSC) and give rise to platelets. However, the authors fall short in recognizing the role of MK-derived platelets in RA.
  Wang Y et al. identified increased MKs in peripheral blood of RA using single-cell RNA sequencing and flow cytometry approaches. They provide clues that MKs act as specific endogenous antigen-presenting cells (APCs), triggering the initial autoimmune T cell for RA pathogenesis1. Of note, novel evidence suggests that MKs derived from bone marrow (BM), lung2 and liver3, instead serve as immunomodulatory or secretory cells4. The generation of platelets is the primary function of MKs.
  Indeed, many characteristics and roles of platelets inherit from MKs. For example, once activated, platelets present antigens via MHC class I molecules (MHC-I) derived from parent MKs5; in this way, the immunogenic information can be conveyed to platelets. Similarly, platelets can also act as an essential immune effector in RA6. An array of platelet surface receptors is responsible for activation, adhesion, and thrombus formation via initiating a complex network of signaling pathways in the presence of ligands. In addition, it is well known that ligands for platelet receptors such as collagen, fibrinogen, serotonin, ADP, and pro-inflammatory molecules are dysregulated in RA6, leading to an increased interaction with platelet receptors. This elevated cascade reaction allows platelets and their microparticles to become pro-inflammatory entities themselves, modulate immune cells, and then influence disease activity. Hence, we presumed that MK could promote RA in a platelet-dependent or/and independent manner.
  In conclusion, we appreciate the work of Wang, Y. et al. for providing new insight into the potential pathogenesis of patients with RA. We suggest that considering the platelet as a potential concern for MK expansion may give clinicians one more light on treatment in the future.

  Reference
  1. Wang Y, Xie X, Zhang C, et al. Rheumatoid arthritis, systemic lupus erythematosus and primary Sjogren's syndrome shared megakaryocyte expansion in peripheral blood. Annals of the rheumatic diseases 2021 doi: 10.1136/annrheumdis-2021-220066 [published Online First: 2021/09/01]
  2. Pariser DN, Hilt ZT, Ture SK, et al. Lung megakaryocytes are immune modulatory cells. The Journal of clinical investigation 2021;131(1) doi: 10.1172/JCI137377 [published Online First: 2020/10/21]
  3. Wang H, He J, Xu C, et al. Decoding Human Megakaryocyte Development. Cell Stem Cell 2021;28(3):535-49 e8. doi: 10.1016/j.stem.2020.11.006 [published Online First: 2020/12/20]
  4. Tilburg J, Becker IC, Italiano JE. Don't you forget about me(gakaryocytes). Blood 2021 doi: 10.1182/blood.2020009302 [published Online First: 2021/09/29]
  5. Marcoux G, Laroche A, Hasse S, et al. Platelet EVs contain an active proteasome involved in protein processing for antigen presentation via MHC-I molecules. Blood 2021 doi: 10.1182/blood.2020009957 [published Online First: 2021/07/23]
  6. Olumuyiwa-Akeredolu OO, Page MJ, Soma P, et al. Platelets: emerging facilitators of cellular crosstalk in rheumatoid arthritis. Nat Rev Rheumatol 2019;15(4):237-48. doi: 10.1038/s41584-019-0187-9 [published Online First: 2019/03/03]

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  Conflict of Interest:
  None declared.

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