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February 2024

Eosinophils identified as a major contributor to bone homeostasis via eosinophil peroxidase activity

Article: Eosinophils preserve bone homeostasis by inhibiting excessive osteoclast formation and activity via eosinophil peroxidase
Andreev, D., Kachler, K., Liu, M. et al
Nat Commun 15, 1067 (2024)

Reviewed by Nana-Fatima Haruna, PhD Candidate, Northwestern University, Chicago, United States

Only recently has the field of immunology begun to appreciate the functional diversity of eosinophils during steady-state homeostatic conditions. There remains a significant gap in our knowledge of the roles and mechanisms utilized by eosinophils to perform their homeostatic functions in different tissues.

The localization of eosinophils within the bone marrow has been a suspected mechanism utilized by eosinophils to perform homeostatic functions. Within the bone marrow, eosinophils colocalize with plasma cells and contribute to their survival (Chu et al., Nat Immunol. 2011 Feb;12(2):151-9). Similarly, the authors of this paper show localization of eosinophils with osteoclasts within the bone marrow. To completely assess bone formation rate, the authors evaluated osteoclast surface (osteoclast surface per bone surface). Quantification of osteoclast surface and cell number provides information on the bone resorption activity of the cell at a given time. Their data showed a significant reduction in bone mass as well as an increase in osteoclast surface and number in eosinophil-deficient ΔdblGATA mice. IL-5 transgenic mice, displaying hyper-eosinophilic phenotype, showed increased bone mass and reduced osteoclast surface and number, indicating a direct relationship between eosinophils and steady-state bone marrow remodeling.

Bulk RNA seq of osteoclasts co-cultured with eosinophils or eosinophil supernatants revealed downregulation of genes involved in osteoclast signaling while upregulating phagocytosis pathways. Eosinophil heme peroxidase, EPX, is internalized by osteoclast precursors, impairing RANKL-mediated signaling thereby inhibiting osteoclast activation. EPX significantly reduced mitochondrial reactive oxygen species in osteoclast precursors. In vivo mouse experiments showed the ability of EPX to successfully resolve inflammation-associated bone loss by reducing the surface and number of mature osteoclasts, thereby preventing excessive bone resorption by osteoclasts. The authors observed a positive correlation between trabecular bone mass and eosinophil counts as well as eosinophil cationic protein levels in rheumatoid arthritis patients, indicating that eosinophil could also be involved in regulating bone homeostasis in humans.

Taken together, this paper expands the field’s understanding of the homeostatic role of eosinophils within the bone marrow and highlights EPX as a key driver in eosinophil-dependent regulation of bone homeostasis. The study also draws attention to the importance of eosinophil spatial organization within tissue microenvironments in providing insight into their tissue-resident functions.

Nana-fatima Haruna is a Ph.D. candidate under the supervision of Dr. Sergejs Berdnikovs at Northwestern University in Chicago. She is currently investigating eosinophil emergency hematopoiesis at sites of inflammation. Nana is interested in utilizing a systems biology approach to understanding eosinophil biology in health and inflammatory conditions. Before joining the Berdnikovs lab, she worked as an application scientist in a biotech company at the New Jersey Bioscience Center, researching the extracellular matrix and the impact of tissue microenvironment on cell behavior. Nana serves on the IES Outreach and Diversity Committee and the Website/Social Media Committee.

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