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Tytuł pozycji:

Asymmetric cell division shapes naive and virtual memory T-cell immunity during ageing.

Tytuł:
Asymmetric cell division shapes naive and virtual memory T-cell immunity during ageing.
Autorzy:
Borsa M; Institute of Microbiology, ETH Zürich, Zurich, Switzerland.; Medical Sciences Division, NDORMS, Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK.
Barandun N; Institute of Microbiology, ETH Zürich, Zurich, Switzerland.
Gräbnitz F; Institute of Microbiology, ETH Zürich, Zurich, Switzerland.
Barnstorf I; Institute of Microbiology, ETH Zürich, Zurich, Switzerland.
Baumann NS; Institute of Microbiology, ETH Zürich, Zurich, Switzerland.
Pallmer K; Institute of Microbiology, ETH Zürich, Zurich, Switzerland.
Baumann S; Institute of Microbiology, ETH Zürich, Zurich, Switzerland.
Stark D; Institute of Microbiology, ETH Zürich, Zurich, Switzerland.
Balaz M; Institute of Food Nutrition and Health, ETH Zürich, Schwerzenbach, Switzerland.
Oetiker N; Institute of Microbiology, ETH Zürich, Zurich, Switzerland.
Wagen F; Institute of Microbiology, ETH Zürich, Zurich, Switzerland.
Wolfrum C; Institute of Food Nutrition and Health, ETH Zürich, Schwerzenbach, Switzerland.
Simon AK; Medical Sciences Division, NDORMS, Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK.
Joller N; Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
Barral Y; Institute of Biochemistry, ETH Zürich, Zurich, Switzerland.
Spörri R; Institute of Microbiology, ETH Zürich, Zurich, Switzerland.
Oxenius A; Institute of Microbiology, ETH Zürich, Zurich, Switzerland. .
Źródło:
Nature communications [Nat Commun] 2021 May 11; Vol. 12 (1), pp. 2715. Date of Electronic Publication: 2021 May 11.
Typ publikacji:
Journal Article; Research Support, Non-U.S. Gov't
Język:
English
Imprint Name(s):
Original Publication: [London] : Nature Pub. Group
MeSH Terms:
Aging/*genetics
Asymmetric Cell Division/*genetics
CD8-Positive T-Lymphocytes/*immunology
Immunologic Memory/*genetics
TOR Serine-Threonine Kinases/*genetics
Aging/immunology ; Animals ; Asymmetric Cell Division/immunology ; CD8-Positive T-Lymphocytes/cytology ; CD8-Positive T-Lymphocytes/drug effects ; Cell Proliferation/drug effects ; Gene Expression Regulation ; Immunity, Innate ; Interferon-gamma/genetics ; Interferon-gamma/immunology ; Interleukin-1beta/genetics ; Interleukin-1beta/immunology ; Interleukin-2 Receptor beta Subunit/genetics ; Interleukin-2 Receptor beta Subunit/immunology ; Lectins, C-Type/genetics ; Lectins, C-Type/immunology ; Lymphocyte Activation ; Mice ; NK Cell Lectin-Like Receptor Subfamily K/genetics ; NK Cell Lectin-Like Receptor Subfamily K/immunology ; Receptors, CXCR3/genetics ; Receptors, CXCR3/immunology ; Receptors, Immunologic/genetics ; Receptors, Immunologic/immunology ; Receptors, Interleukin-7/genetics ; Receptors, Interleukin-7/immunology ; Signal Transduction ; Sirolimus/pharmacology ; TOR Serine-Threonine Kinases/antagonists & inhibitors ; TOR Serine-Threonine Kinases/immunology
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Grant Information:
103830/Z/14/Z United Kingdom WT_ Wellcome Trust
Substance Nomenclature:
0 (Cxcr3 protein, mouse)
0 (IL1B protein, mouse)
0 (Il2rb protein, mouse)
0 (Interleukin-1beta)
0 (Interleukin-2 Receptor beta Subunit)
0 (Klrg1 protein, mouse)
0 (Klrk1 protein, mouse)
0 (Lectins, C-Type)
0 (NK Cell Lectin-Like Receptor Subfamily K)
0 (Receptors, CXCR3)
0 (Receptors, Immunologic)
0 (Receptors, Interleukin-7)
82115-62-6 (Interferon-gamma)
EC 2.7.1.1 (mTOR protein, mouse)
EC 2.7.11.1 (TOR Serine-Threonine Kinases)
W36ZG6FT64 (Sirolimus)
Entry Date(s):
Date Created: 20210512 Date Completed: 20210527 Latest Revision: 20211204
Update Code:
20240105
PubMed Central ID:
PMC8113513
DOI:
10.1038/s41467-021-22954-y
PMID:
33976157
Czasopismo naukowe
Efficient immune responses rely on heterogeneity, which in CD8 + T cells, amongst other mechanisms, is achieved by asymmetric cell division (ACD). Here we find that ageing, known to negatively impact immune responses, impairs ACD in murine CD8 + T cells, and that this phenotype can be rescued by transient mTOR inhibition. Increased ACD rates in mitotic cells from aged mice restore the expansion and memory potential of their cellular progenies. Further characterization of the composition of CD8 + T cells reveals that virtual memory cells (T VM cells), which accumulate during ageing, have a unique proliferation and metabolic profile, and retain their ability to divide asymmetrically, which correlates with increased memory potential. The opposite is observed for naive CD8 + T cells from aged mice. Our data provide evidence on how ACD modulation contributes to long-term survival and function of T cells during ageing, offering new insights into how the immune system adapts to ageing.

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