Lymphopoiesis is attenuated upon hepatocyte-specific deletion of the cytochrome c oxidase assembly factor Sco1
Date
2025-04
Authors
Pioli, KimAnh T.
Ghosh, Sampurna
Boulet, Aren
Leary, Scot C.
Pioli, Peter
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Cell Press
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Article
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Abstract
Mutations that negatively impact mitochondrial function are highly prevalent in humans and lead to disorders with a wide spectrum of disease phenotypes, including deficiencies in immune cell development and/or function. Previous analyses of mice with a hepatocyte-specific cytochrome c oxidase (COX) deficiency revealed an unexpected peripheral blood leukopenia associated with splenic and thymic atrophy. Here, we use mice with a hepatocyte-specific deletion of the COX assembly factor Sco1 to show that metabolic defects extrinsic to the hematopoietic compartment lead to a pan-lymphopenia represented by severe losses in both B and T cells. We further demonstrate that immune defects in these mice are associated with the loss of bone marrow lymphoid progenitors common to both lineages and early signs of autoantibody-mediated autoimmunity. Our findings collectively identify hepatocyte dysfunction as a potential instigator of immunodeficiency in patients with congenital mitochondrial defects who suffer from chronic or recurrent infections.
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Keywords
mutations, COX assembly factor Sco1, lymphopenia
Citation
Pioli, K. T., Ghosh, S., Boulet, A., Leary, S. C., & Pioli, P. D. (2025). Lymphopoiesis is attenuated upon hepatocyte-specific deletion of the cytochrome c oxidase assembly factor Sco1. iScience, 28(4), 112151-. https://doi.org/10.1016/j.isci.2025.112151
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DOI
https://doi.org/10.1016/j.isci.2025.112151