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TP53INP1 deficiency maintains murine B lymphopoiesis in aged bone marrow through redox-controlled IL-7R/STAT5 signaling

Abstract : Bone marrow (BM) produces all blood and immune cells deriving from hematopoietic stem cells (HSCs). The decrease of immune cell production during aging is one of the features of immunosenes-cence. The impact of redox dysregulation in BM aging is still poorly understood. Here we use TP53INP1-deficient (KO) mice endowed with chronic oxidative stress to assess the influence of aging-associated redox alterations in BM homeostasis. We show that TP53INP1 deletion has no impact on aging-related accumulation of HSCs. In contrast, the aging-related contraction of the lymphoid compartment is mitigated in TP53INP1 KO mice. B cells that accumulate in old KO BM are differentiating cells that can mature into functional B cells. Importantly, this phenotype results from B cell-intrinsic events associated with defective redox control. Finally, we show that oxidative stress in aged TP53INP1-deficient mice maintains STAT5 expression and activation in early B cells, driving high Pax5 expression, which provides a molecular mechanism for maintenance of B cell development upon aging.
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https://hal.archives-ouvertes.fr/hal-02145737
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Submitted on : Monday, June 3, 2019 - 11:45:29 AM
Last modification on : Wednesday, November 17, 2021 - 11:08:06 AM

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Bochra Zidi, Christelle Vincent-Fabert, Laurent Pouyet, Marion Seillier, Amelle Vandevelde, et al.. TP53INP1 deficiency maintains murine B lymphopoiesis in aged bone marrow through redox-controlled IL-7R/STAT5 signaling. Proceedings of the National Academy of Sciences of the United States of America , National Academy of Sciences, 2019, 116 (1), pp.211-216. ⟨10.1073/pnas.1809980116⟩. ⟨hal-02145737⟩

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