Microbiota-Derived Propionate Modulates Megakaryopoiesis and Platelet Function

Dürholz K, Schmid E, Frech M, Azizov V, Otterbein N, Lucas S, Rauh M, Schett G, Bruns H, Zaiss M (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Frontiers in Immunology Frontiers Research Foundation / Frontiers Media

Book Volume: 13

Article Number: 908174

DOI: 10.3389/fimmu.2022.908174

Abstract

Rheumatoid arthritis (RA) is associated with an increased risk for cardiovascular events driven by abnormal platelet clotting effects. Platelets are produced by megakaryocytes, deriving from megakaryocyte erythrocyte progenitors (MEP) in the bone marrow. Increased megakaryocyte expansion across common autoimmune diseases was shown for RA, systemic lupus erythematosus (SLE) and primary Sjögren’s syndrome (pSS). In this context, we evaluated the role of the microbial-derived short chain fatty acid (SCFA) propionate on hematopoietic progenitors in the collagen induced inflammatory arthritis model (CIA) as we recently showed attenuating effects of preventive propionate treatment on CIA severity. In vivo, propionate treatment starting 21 days post immunization (dpi) reduced the frequency of MEPs in the bone marrow of CIA and naïve mice. Megakaryocytes numbers were reduced but increased the expression of the maturation marker CD61. Consistent with this, functional analysis of platelets showed an upregulated reactivity state following propionate-treatment. This was confirmed by elevated histone 3 acetylation and propionylation as well as by RNAseq analysis in Meg-01 cells. Taken together, we identified a novel nutritional axis that skews platelet formation and function.

Authors with CRIS profile

Kerstin Dürholz Department of Medicine 3 – Rheumatology and Immunology Eva Schmid Department of Medicine 3 – Rheumatology and Immunology Michael Frech Department of Medicine 3 – Rheumatology and Immunology Vugar Azizov Department of Medicine 3 – Rheumatology and Immunology Sébastien Lucas Department of Medicine 3 – Rheumatology and Immunology Manfred Rauh Department of Paediatrics and Adolescent Medicine Georg Schett Lehrstuhl für Innere Medizin III Heiko Bruns Department of Medicine 5 – Haematology and Oncology Mario Zaiss Department of Medicine 3 – Rheumatology and Immunology

How to cite

APA:

Dürholz, K., Schmid, E., Frech, M., Azizov, V., Otterbein, N., Lucas, S.,... Zaiss, M. (2022). Microbiota-Derived Propionate Modulates Megakaryopoiesis and Platelet Function. Frontiers in Immunology, 13. https://doi.org/10.3389/fimmu.2022.908174

MLA:

Dürholz, Kerstin, et al. "Microbiota-Derived Propionate Modulates Megakaryopoiesis and Platelet Function." Frontiers in Immunology 13 (2022).

BibTeX: Download