TP53INP1 Deficiency Maintains Murine B Lymphopoiesis in Aged Bone Marrow Through Redox-controlled IL-7R/STAT5 Signaling

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2018 Dec 19

PMID 30559202

Citations 8

Authors

Bochra Zidi

Christelle Vincent-Fabert

Laurent Pouyet

Marion Seillier

Amelle Vandevelde

Prudence Nguessan

Mathilde Poplineau

Geoffrey Guittard

Stephane J C Mancini

Estelle Duprez

Alice Carrier

Affiliations

Soon will be listed here.

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 immunosenescence. 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 expression, which provides a molecular mechanism for maintenance of B cell development upon aging.

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