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Article ; Online: Early precursor T cells establish and propagate T cell exhaustion in chronic infection.

Utzschneider, Daniel T / Gabriel, Sarah S / Chisanga, David / Gloury, Renee / Gubser, Patrick M / Vasanthakumar, Ajithkumar / Shi, Wei / Kallies, Axel

Nature immunology

2020 Volume 21, Issue 10, Page(s) 1256–1266

Abstract: ... ...

Abstract	CD8
MeSH term(s)	Animals ; CD8-Positive T-Lymphocytes/immunology ; Cell Differentiation ; Cell Self Renewal ; Cells, Cultured ; Chronic Disease ; Clonal Anergy ; Epigenesis, Genetic ; Hepatocyte Nuclear Factor 1-alpha/metabolism ; Immune Tolerance ; Lymphocytic Choriomeningitis/immunology ; Lymphocytic choriomeningitis virus/physiology ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Precursor Cells, T-Lymphoid/immunology ; Receptors, Antigen, T-Cell/metabolism ; T-Cell Antigen Receptor Specificity
Chemical Substances	Hepatocyte Nuclear Factor 1-alpha ; Hnf1a protein, mouse ; Receptors, Antigen, T-Cell
Keywords	covid19
Language	English
Publishing date	2020-08-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2016987-5
ISSN	1529-2916 ; 1529-2908
ISSN (online)	1529-2916
ISSN	1529-2908
DOI	10.1038/s41590-020-0760-z
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Increased lipid metabolism impairs NK cell function and mediates adaptation to the lymphoma environment.

Kobayashi, Takumi / Lam, Pui Yeng / Jiang, Hui / Bednarska, Karolina / Gloury, Renee / Murigneux, Valentine / Tay, Joshua / Jacquelot, Nicolas / Li, Rui / Tuong, Zewen Kelvin / Leggatt, Graham R / Gandhi, Maher K / Hill, Michelle M / Belz, Gabrielle T / Ngo, Shyuan / Kallies, Axel / Mattarollo, Stephen R

Blood

2021 Volume 136, Issue 26, Page(s) 3004–3017

Abstract: Natural killer (NK) cells play critical roles in protection against hematological malignancies but can acquire a dysfunctional state, which limits antitumor immunity. However, the underlying reasons for this impaired NK cell function remain to be ... ...

Abstract	Natural killer (NK) cells play critical roles in protection against hematological malignancies but can acquire a dysfunctional state, which limits antitumor immunity. However, the underlying reasons for this impaired NK cell function remain to be uncovered. We found that NK cells in aggressive B-cell lymphoma underwent substantial transcriptional reprogramming associated with increased lipid metabolism, including elevated expression of the transcriptional regulator peroxisome activator receptor-γ (PPAR-γ). Exposure to fatty acids in the lymphoma environment potently suppressed NK cell effector response and cellular metabolism. NK cells from both diffuse large B-cell lymphoma patients and Eµ-myc B-cell lymphoma-bearing mice displayed reduced interferon-γ (IFN-γ) production. Activation of PPAR-γ partially restored mitochondrial membrane potential and IFN-γ production. Overall, our data indicate that increased lipid metabolism, while impairing their function, is a functional adaptation of NK cells to the fatty-acid rich lymphoma environment.
MeSH term(s)	Animals ; Humans ; Interferon-gamma/genetics ; Interferon-gamma/immunology ; Killer Cells, Natural/immunology ; Killer Cells, Natural/pathology ; Lipid Metabolism/immunology ; Lymphoma, Large B-Cell, Diffuse/genetics ; Lymphoma, Large B-Cell, Diffuse/immunology ; Lymphoma, Large B-Cell, Diffuse/pathology ; Membrane Potential, Mitochondrial/genetics ; Membrane Potential, Mitochondrial/immunology ; Mice ; Mice, Transgenic ; Neoplasm Proteins/genetics ; Neoplasm Proteins/immunology ; PPAR gamma/genetics ; PPAR gamma/immunology ; Tumor Microenvironment/genetics ; Tumor Microenvironment/immunology
Chemical Substances	IFNG protein, mouse ; Neoplasm Proteins ; PPAR gamma ; Pparg protein, mouse ; Interferon-gamma (82115-62-6)
Language	English
Publishing date	2021-04-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood.2020005602
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Zs.MO 364: Show issues

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Article: Early precursor T cells establish and propagate T cell exhaustion in chronic infection

Utzschneider, Daniel T / Gabriel, Sarah S / Chisanga, David / Gloury, Renee / Gubser, Patrick M / Vasanthakumar, Ajithkumar / Shi, Wei / Kallies, Axel

Abstract: CD8+ T cells responding to chronic infections or tumors acquire an 'exhausted' state associated with elevated expression of inhibitory receptors, including PD-1, and impaired cytokine production. Exhausted T cells are continuously replenished by T cells ... ...

Abstract	CD8+ T cells responding to chronic infections or tumors acquire an 'exhausted' state associated with elevated expression of inhibitory receptors, including PD-1, and impaired cytokine production. Exhausted T cells are continuously replenished by T cells with precursor characteristics that self-renew and depend on the transcription factor TCF1; however, their developmental requirements are poorly understood. In the present study, we demonstrate that high antigen load promoted the differentiation of precursor T cells, which acquired hallmarks of exhaustion within days of infection, whereas early effector cells retained polyfunctional features. Early precursor T cells showed epigenetic imprinting characteristic of T cell receptor-dependent transcription factor binding and were restricted to the generation of cells displaying exhaustion characteristics. Transcription factors BACH2 and BATF were key regulators with opposing functions in the generation of early precursor T cells. Overall, we demonstrate that exhaustion manifests first in TCF1+ precursor T cells and is propagated subsequently to the pool of antigen-specific T cells.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #32839610
Database	COVID19

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Article ; Online: Author Correction: Sex-specific adipose tissue imprinting of regulatory T cells.

Vasanthakumar, Ajithkumar / Chisanga, David / Blume, Jonas / Gloury, Renee / Britt, Kara / Henstridge, Darren C / Zhan, Yifan / Torres, Santiago Valle / Liene, Sebastian / Collins, Nicholas / Cao, Enyuan / Sidwell, Tom / Li, Chaoran / Spallanzani, Raul German / Liao, Yang / Beavis, Paul A / Gebhardt, Thomas / Trevaskis, Natalie / Nutt, Stephen L /

Zajac, Jeffrey D / Davey, Rachel A / Febbraio, Mark A / Mathis, Diane / Shi, Wei / Kallies, Axel

Nature

2021 Volume 591, Issue 7851, Page(s) E26

Language	English
Publishing date	2021-02-16
Publishing country	England
Document type	Published Erratum
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/s41586-020-2251-7
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Zs.A 26: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Attenuation of TCR-induced transcription by Bach2 controls regulatory T cell differentiation and homeostasis.

Sidwell, Tom / Liao, Yang / Garnham, Alexandra L / Vasanthakumar, Ajithkumar / Gloury, Renee / Blume, Jonas / Teh, Peggy P / Chisanga, David / Thelemann, Christoph / de Labastida Rivera, Fabian / Engwerda, Christian R / Corcoran, Lynn / Kometani, Kohei / Kurosaki, Tomohiro / Smyth, Gordon K / Shi, Wei / Kallies, Axel

Nature communications

2020 Volume 11, Issue 1, Page(s) 252

Abstract: Differentiation and homeostasis of ... ...

Abstract	Differentiation and homeostasis of Foxp3
MeSH term(s)	Animals ; Basic-Leucine Zipper Transcription Factors/deficiency ; Basic-Leucine Zipper Transcription Factors/metabolism ; Cell Differentiation/immunology ; Chromatin/metabolism ; Colitis/immunology ; Disease Models, Animal ; Epigenesis, Genetic/immunology ; Forkhead Transcription Factors/metabolism ; Gastrointestinal Tract/immunology ; Gene Expression Regulation/immunology ; Homeostasis/immunology ; Interferon Regulatory Factors/deficiency ; Interferon Regulatory Factors/metabolism ; Interleukin-10/biosynthesis ; Lymphocyte Activation ; Mice ; Mice, Inbred C57BL ; Mice, Mutant Strains ; Receptors, Antigen, T-Cell/metabolism ; Signal Transduction/immunology ; T-Lymphocyte Subsets/immunology ; T-Lymphocyte Subsets/metabolism ; T-Lymphocytes, Regulatory/immunology ; T-Lymphocytes, Regulatory/metabolism
Chemical Substances	Bach2 protein, mouse ; Basic-Leucine Zipper Transcription Factors ; Chromatin ; Forkhead Transcription Factors ; Foxp3 protein, mouse ; IL10 protein, mouse ; Interferon Regulatory Factors ; Receptors, Antigen, T-Cell ; interferon regulatory factor-4 ; Interleukin-10 (130068-27-8)
Language	English
Publishing date	2020-01-14
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-019-14112-2
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Attenuation of TCR-induced transcription by Bach2 controls regulatory T cell differentiation and homeostasis

Tom Sidwell / Yang Liao / Alexandra L. Garnham / Ajithkumar Vasanthakumar / Renee Gloury / Jonas Blume / Peggy P. Teh / David Chisanga / Christoph Thelemann / Fabian de Labastida Rivera / Christian R. Engwerda / Lynn Corcoran / Kohei Kometani / Tomohiro Kurosaki / Gordon K. Smyth / Wei Shi / Axel Kallies

Nature Communications, Vol 11, Iss 1, Pp 1-

2020 Volume 17

Abstract: The transcription factor Bach2 is critical for T cell differentiation, but how it functions in Treg cells is unclear. Here the authors use a Treg-specific mouse model to show that Bach2 controls homeostasis and function of Treg cells by limiting DNA ... ...

Abstract	The transcription factor Bach2 is critical for T cell differentiation, but how it functions in Treg cells is unclear. Here the authors use a Treg-specific mouse model to show that Bach2 controls homeostasis and function of Treg cells by limiting DNA accessibility and activity of IRF4 in response to TCR signaling.
Keywords	Science ; Q
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Transcription Factor T-bet in B Cells Modulates Germinal Center Polarization and Antibody Affinity Maturation in Response to Malaria.

Ly, Ann / Liao, Yang / Pietrzak, Halina / Ioannidis, Lisa J / Sidwell, Tom / Gloury, Renee / Doerflinger, Marcel / Triglia, Tony / Qin, Raymond Z / Groom, Joanna R / Belz, Gabrielle T / Good-Jacobson, Kim L / Shi, Wei / Kallies, Axel / Hansen, Diana S

Cell reports

2019 Volume 29, Issue 8, Page(s) 2257–2269.e6

Abstract: Despite the key role that antibodies play in protection, the cellular processes mediating the acquisition of humoral immunity against malaria are not fully understood. Using an infection model of severe malaria, we find that germinal center (GC) B cells ... ...

Abstract	Despite the key role that antibodies play in protection, the cellular processes mediating the acquisition of humoral immunity against malaria are not fully understood. Using an infection model of severe malaria, we find that germinal center (GC) B cells upregulate the transcription factor T-bet during infection. Molecular and cellular analyses reveal that T-bet in B cells is required not only for IgG
MeSH term(s)	Animals ; Antibody Affinity/genetics ; Antibody Affinity/physiology ; B-Lymphocytes/metabolism ; Germinal Center/cytology ; Germinal Center/metabolism ; Malaria/immunology ; Malaria/metabolism ; Mice ; Mice, Inbred C57BL ; Mutation/genetics ; RGS Proteins/genetics ; RGS Proteins/metabolism ; Receptors, CXCR3/genetics ; Receptors, CXCR3/metabolism ; T-Box Domain Proteins/genetics ; T-Box Domain Proteins/metabolism
Chemical Substances	RGS Proteins ; Receptors, CXCR3 ; T-Box Domain Proteins ; T-box transcription factor TBX21
Language	English
Publishing date	2019-11-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2019.10.087
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Antigen-driven EGR2 expression is required for exhausted CD8

Wagle, Mayura V / Vervoort, Stephin J / Kelly, Madison J / Van Der Byl, Willem / Peters, Timothy J / Martin, Ben P / Martelotto, Luciano G / Nüssing, Simone / Ramsbottom, Kelly M / Torpy, James R / Knight, Deborah / Reading, Sinead / Thia, Kevin / Miosge, Lisa A / Howard, Debbie R / Gloury, Renee / Gabriel, Sarah S / Utzschneider, Daniel T / Oliaro, Jane /

Powell, Jonathan D / Luciani, Fabio / Trapani, Joseph A / Johnstone, Ricky W / Kallies, Axel / Goodnow, Christopher C / Parish, Ian A

Nature communications

2021 Volume 12, Issue 1, Page(s) 2782

Abstract: Chronic stimulation of ... ...

Abstract	Chronic stimulation of CD8
MeSH term(s)	Animals ; Antigens/immunology ; CD4-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/pathology ; Clonal Anergy/immunology ; Early Growth Response Protein 2/biosynthesis ; Early Growth Response Protein 2/metabolism ; Lymphopoiesis/physiology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout
Chemical Substances	Antigens ; Early Growth Response Protein 2 ; Egr2 protein, mouse
Language	English
Publishing date	2021-05-13
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-021-23044-9
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Sex-specific adipose tissue imprinting of regulatory T cells.

Zajac, Jeffrey D / Davey, Rachel A / Febbraio, Mark A / Mathis, Diane / Shi, Wei / Kallies, Axel

Nature

2020 Volume 579, Issue 7800, Page(s) 581–585

Abstract: Adipose tissue is an energy store and a dynamic endocrine ... ...

Abstract	Adipose tissue is an energy store and a dynamic endocrine organ
MeSH term(s)	Androgens/metabolism ; Animals ; Chemokine CCL2/immunology ; Chromatin/genetics ; Female ; Gene Expression Regulation ; Gonadal Steroid Hormones/metabolism ; Inflammation/immunology ; Inflammation/metabolism ; Interleukin-33/immunology ; Intra-Abdominal Fat/immunology ; Intra-Abdominal Fat/metabolism ; Male ; Mice ; Positive Regulatory Domain I-Binding Factor 1/metabolism ; RNA-Seq ; Receptors, CCR2/metabolism ; Sex Characteristics ; Stromal Cells/cytology ; Stromal Cells/immunology ; Stromal Cells/metabolism ; T-Lymphocytes, Regulatory/immunology ; T-Lymphocytes, Regulatory/metabolism ; Transcription, Genetic
Chemical Substances	Androgens ; Ccl2 protein, mouse ; Ccr2 protein, mouse ; Chemokine CCL2 ; Chromatin ; Gonadal Steroid Hormones ; Interleukin-33 ; Prdm1 protein, mouse ; Receptors, CCR2 ; Positive Regulatory Domain I-Binding Factor 1 (EC 2.1.1.-)
Language	English
Publishing date	2020-02-26
Publishing country	England
Document type	Journal Article
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/s41586-020-2040-3
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Zs.A 26: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Transcription Factor IRF4 Promotes CD8

Man, Kevin / Gabriel, Sarah S / Liao, Yang / Gloury, Renee / Preston, Simon / Henstridge, Darren C / Pellegrini, Marc / Zehn, Dietmar / Berberich-Siebelt, Friederike / Febbraio, Mark A / Shi, Wei / Kallies, Axel

Immunity

2017 Volume 47, Issue 6, Page(s) 1129–1141.e5

Abstract: During chronic stimulation, ... ...

Abstract	During chronic stimulation, CD8
MeSH term(s)	Animals ; Basic-Leucine Zipper Transcription Factors/genetics ; Basic-Leucine Zipper Transcription Factors/immunology ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/virology ; Cell Differentiation ; Gene Expression Regulation ; HEK293 Cells ; Hepatocyte Nuclear Factor 1-alpha/genetics ; Hepatocyte Nuclear Factor 1-alpha/immunology ; Humans ; Immunologic Memory ; Interferon Regulatory Factors/deficiency ; Interferon Regulatory Factors/genetics ; Interferon Regulatory Factors/immunology ; Lymphocyte Activation ; Lymphocyte Depletion ; Lymphocytic Choriomeningitis/genetics ; Lymphocytic Choriomeningitis/immunology ; Lymphocytic Choriomeningitis/virology ; Lymphocytic choriomeningitis virus/growth & development ; Lymphocytic choriomeningitis virus/immunology ; Mice ; Mice, Knockout ; NFATC Transcription Factors/genetics ; NFATC Transcription Factors/immunology ; Programmed Cell Death 1 Receptor/genetics ; Programmed Cell Death 1 Receptor/immunology ; Receptors, Antigen, T-Cell/genetics ; Receptors, Antigen, T-Cell/immunology ; Signal Transduction
Chemical Substances	Basic-Leucine Zipper Transcription Factors ; Batf protein, mouse ; Hepatocyte Nuclear Factor 1-alpha ; Hnf1a protein, mouse ; Interferon Regulatory Factors ; NFATC Transcription Factors ; Nfatc1 protein, mouse ; Pdcd1 protein, mouse ; Programmed Cell Death 1 Receptor ; Receptors, Antigen, T-Cell ; interferon regulatory factor-4
Language	English
Publishing date	2017--19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1217235-2
ISSN	1097-4180 ; 1074-7613
ISSN (online)	1097-4180
ISSN	1074-7613
DOI	10.1016/j.immuni.2017.11.021
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 4227: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 69: Show issues

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