TNFAIP3 Plays a Role in Aging of the Hematopoietic System
Hematopoietic stem and progenitor cells (HSPC) experience a functional decline in response to chronic inflammation or aging. Haploinsufficiency of A20, or TNFAIP3, an innate immune regulator, is associated with a variety of autoimmune, inflammatory, and hematologic malignancies. Based on a prior ana...
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doaj-36c2b55c0df447f497aa91330ee398fb2020-11-25T04:06:56ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-11-011110.3389/fimmu.2020.536442536442TNFAIP3 Plays a Role in Aging of the Hematopoietic SystemMolly A. Smith0Molly A. Smith1Ashley E. Culver-Cochran2Emmalee R. Adelman3Garrett W. Rhyasen4Garrett W. Rhyasen5Averil Ma6Maria E. Figueroa7Maria E. Figueroa8Daniel T. Starczynowski9Daniel T. Starczynowski10Daniel T. Starczynowski11Experimental Hematology and Cancer Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United StatesDepartment of Cancer Biology, University of Cincinnati, Cincinnati, OH, United StatesExperimental Hematology and Cancer Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United StatesDepartment of Human Genetics, University of Miami, Miami, FL, United StatesExperimental Hematology and Cancer Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United StatesDepartment of Cancer Biology, University of Cincinnati, Cincinnati, OH, United StatesDepartment of Medicine, University of California, San Francisco, San Francisco, CA, United StatesDepartment of Human Genetics, University of Miami, Miami, FL, United StatesSylvester Comprehensive Cancer Center, University of Miami, Miami, FL, United StatesExperimental Hematology and Cancer Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United StatesDepartment of Cancer Biology, University of Cincinnati, Cincinnati, OH, United StatesDepartment of Pediatrics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United StatesHematopoietic stem and progenitor cells (HSPC) experience a functional decline in response to chronic inflammation or aging. Haploinsufficiency of A20, or TNFAIP3, an innate immune regulator, is associated with a variety of autoimmune, inflammatory, and hematologic malignancies. Based on a prior analysis of epigenomic and transcriptomic changes during normal human aging, we find that the expression of A20 is significantly reduced in aged HSPC as compared to young HSPC. Here, we show that the partial reduction of A20 expression in young HSPC results in characteristic features of aging. Specifically, heterozygous deletion of A20 in hematopoietic cells resulted in expansion of the HSPC pool, reduced HSPC fitness, and myeloid-biased hematopoiesis. These findings suggest that altered expression of A20 in HSPC contributes to an aging-like phenotype, and that there may be a common underlying mechanism for diminished HSPC function between inflammatory states and aging.https://www.frontiersin.org/articles/10.3389/fimmu.2020.536442/fullhematopoietic (stem) cellsaginginflammationA20 (TNFAIP3)hematopoiesis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Molly A. Smith Molly A. Smith Ashley E. Culver-Cochran Emmalee R. Adelman Garrett W. Rhyasen Garrett W. Rhyasen Averil Ma Maria E. Figueroa Maria E. Figueroa Daniel T. Starczynowski Daniel T. Starczynowski Daniel T. Starczynowski |
spellingShingle |
Molly A. Smith Molly A. Smith Ashley E. Culver-Cochran Emmalee R. Adelman Garrett W. Rhyasen Garrett W. Rhyasen Averil Ma Maria E. Figueroa Maria E. Figueroa Daniel T. Starczynowski Daniel T. Starczynowski Daniel T. Starczynowski TNFAIP3 Plays a Role in Aging of the Hematopoietic System Frontiers in Immunology hematopoietic (stem) cells aging inflammation A20 (TNFAIP3) hematopoiesis |
author_facet |
Molly A. Smith Molly A. Smith Ashley E. Culver-Cochran Emmalee R. Adelman Garrett W. Rhyasen Garrett W. Rhyasen Averil Ma Maria E. Figueroa Maria E. Figueroa Daniel T. Starczynowski Daniel T. Starczynowski Daniel T. Starczynowski |
author_sort |
Molly A. Smith |
title |
TNFAIP3 Plays a Role in Aging of the Hematopoietic System |
title_short |
TNFAIP3 Plays a Role in Aging of the Hematopoietic System |
title_full |
TNFAIP3 Plays a Role in Aging of the Hematopoietic System |
title_fullStr |
TNFAIP3 Plays a Role in Aging of the Hematopoietic System |
title_full_unstemmed |
TNFAIP3 Plays a Role in Aging of the Hematopoietic System |
title_sort |
tnfaip3 plays a role in aging of the hematopoietic system |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2020-11-01 |
description |
Hematopoietic stem and progenitor cells (HSPC) experience a functional decline in response to chronic inflammation or aging. Haploinsufficiency of A20, or TNFAIP3, an innate immune regulator, is associated with a variety of autoimmune, inflammatory, and hematologic malignancies. Based on a prior analysis of epigenomic and transcriptomic changes during normal human aging, we find that the expression of A20 is significantly reduced in aged HSPC as compared to young HSPC. Here, we show that the partial reduction of A20 expression in young HSPC results in characteristic features of aging. Specifically, heterozygous deletion of A20 in hematopoietic cells resulted in expansion of the HSPC pool, reduced HSPC fitness, and myeloid-biased hematopoiesis. These findings suggest that altered expression of A20 in HSPC contributes to an aging-like phenotype, and that there may be a common underlying mechanism for diminished HSPC function between inflammatory states and aging. |
topic |
hematopoietic (stem) cells aging inflammation A20 (TNFAIP3) hematopoiesis |
url |
https://www.frontiersin.org/articles/10.3389/fimmu.2020.536442/full |
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