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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.
Cited literature [47 references]
https://hal.archives-ouvertes.fr/hal-02145737
Contributor : Ghislain Bidaut Connect in order to contact the contributor
Submitted on : Monday, June 3, 2019 - 11:45:29 AM
Last modification on : Wednesday, November 17, 2021 - 11:08:06 AM
Contributor : Ghislain Bidaut Connect in order to contact the contributor
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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Zidi-PNAS2019.pdf
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