Plasticity and lineage commitment of individual TH1 cells are determined by stable T-bet expression quantities

被引：2

作者：

Hegazy, Ahmed N. ^{[1
,2
,3
,4
,5
]}

Peine, Caroline ^{[6
,7
]}

Niesen, Dominik ^{[6
,7
]}

Panse, Isabel ^{[6
,7
]}

Vainshtein, Yevhen ^{[1
,2
,8
,9
]}

Kommer, Christoph ^{[1
,2
,8
,9
]}

Zhang, Qin ^{[1
,2
,8
,9
]}

Brunner, Tobias M. ^{[6
,7
]}

Peine, Michael ^{[6
,7
]}

Froehlich, Anja ^{[6
,7
]}

Ishaque, Naveed ^{[1
,2
,8
,9
]}

Marek, Roman M. ^{[6
,7
]}

Zhu, Jinfang ^{[10
]}

Hoefer, Thomas ^{[1
,2
,8
,9
]}

Loehning, Max ^{[6
,7
]}

机构：

[1] Charite Univ Med Berlin, D-12203 Berlin, Germany

[2] Free Univ Berlin, D-12203 Berlin, Germany

[3] Humboldt Univ, Med Dept Gastroenterol Infect Dis & Rheumatol, D-12203 Berlin, Germany

[4] German Rheumatism Res Ctr DRFZ, Leibniz Inst, Inflammatory Mech, D-10117 Berlin, Germany

[5] Charite Univ Med Berlin, Berlin Inst Hlth BIH, D-10117 Berlin, Germany

[6] Humboldt Univ, Dept Rheumatol & Clin Immunol, Expt Immunol & Osteoarthritis Res, D-10117 Berlin, Germany

[7] German Rheumatism Res Ctr DRFZ, Leibniz Inst, Pitzer Lab Osteoarthritis Res, D-10117 Berlin, Germany

[8] German Canc Res Ctr, Div Theoret Syst Biol, D-69120 Heidelberg, Germany

[9] Heidelberg Univ, Bioquant Ctr, D-69120 Heidelberg, Germany

[10] Natl Inst Allergy & Infect Dis, Lab Immune Syst Biol, NIH, Bethesda, MD 20892 USA

来源：

SCIENCE ADVANCES | 2024年 / 10卷 / 23期

基金：

美国国家科学基金会; 美国国家卫生研究院;

关键词：

IFN-GAMMA PRODUCTION; MEMORY; DIFFERENTIATION; EFFECTOR; MICE; MECHANISMS; VIRUS; IL-10; NAIVE; LYMPHOCYTES;

D O I：

10.1126/sciadv.adk2693

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

T helper 1 (T(H)1) cell identity is defined by the expression of the lineage-specifying transcription factor T-bet. Here, we examine the influence of T-bet expression heterogeneity on subset plasticity by leveraging cell sorting of distinct in vivo-differentiated T(H)1 cells based on their quantitative expression of T-bet and interferon-gamma. Heterogeneous T-bet expression states were regulated by virus-induced type I interferons and were stably maintained even after secondary viral infection. Exposed to alternative differentiation signals, the sorted subpopulations exhibited graded levels of plasticity, particularly toward the T(H)2 lineage: T-bet quantities were inversely correlated with the ability to express the T(H)2 lineage-specifying transcription factor GATA-3 and T(H)2 cytokines. Reprogramed T(H)1 cells acquired graded mixed T(H)1 + T(H)2 phenotypes with a hybrid epigenetic landscape. Continuous presence of T-bet in differentiated T(H)1 cells was essential to ensure T(H)1 cell stability. Thus, innate cytokine signals regulate T(H)1 cell plasticity via an individual cell-intrinsic rheostat to enable T cell subset adaptation to subsequent challenges.

引用

页数：15

共 50 条

[31] Tet2 deletion in CD4+T cells disrupts Th1 lineage commitment in memory cells and enhances T follicular helper cell recall responses to viral rechallenge
Baessler, Andrew
Fuchs, Bryce
Perkins, Bryant
Richens, Andrew W.
Novis, Camille L.
Harrison-Chau, Malia
Sircy, Linda M.
Thiede, Kendall A.
Hale, J. Scott
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2023, 120 (36)
[32] Impaired T cell activation and increased Th2 lineage commitment in Annexin-1-deficient T cells
D'Acquisto, Fulvio
Paschalidis, Nikolaos
Sampaio, Andre L. F.
Merghani, Ahmed
Flower, Roderick J.
Perretti, Mauro
EUROPEAN JOURNAL OF IMMUNOLOGY, 2007, 37 (11) : 3131 - 3142
[33] T-bet- and STAT4-dependent IL-33 receptor expression directly promotes antiviral Th1 cell responses
Baumann, Claudia
Bonilla, Weldy V.
Froehlich, Anja
Helmstetter, Caroline
Peine, Michael
Hegazy, Ahmed N.
Pinschewer, Daniel D.
Loehning, Max
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2015, 112 (13) : 4056 - 4061
[34] Human B cells promote T-cell plasticity to optimize antibody response by inducing coexpression of TH1/TFH signatures
de Wit, Jelle
Jorritsma, Tineke
Makuch, Mateusz
Remmerswaal, Ester B. M.
Bos, Hanny Klaasse
Souwer, Yuri
Neefjes, Jacques
ten Berge, Ineke J. M.
van Ham, S. Marieke
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2015, 135 (04) : 1053 - 1060
[35] Core 2 β1,6-N-acetylglucosaminyltransferase-I, crucial for P-selectin ligand expression is controlled by a distal enhancer regulated by STAT4 and T-bet in CD4+T helper cells 1
Mardahl, Maibritt
Schroeter, Micha F.
Engelbert, Dirk
Pink, Matthias
Sperandio, Markus
Hamann, Alf
Syrbe, Uta
MOLECULAR IMMUNOLOGY, 2016, 77 : 132 - 140
[36] T-bet-Expressing B Cells Are Positively Associated with Crohn's Disease Activity and Support Th1 Inflammation
Wang, Zhenlong
Wang, Zhiming
Wang, Jinjing
Diao, Yanqing
Qian, Xiaoli
Zhu, Nan
DNA AND CELL BIOLOGY, 2016, 35 (10) : 628 - 635
[37] The T(H)1 cell lineage-determining transcription factor T-bet suppresses T(H)2 gene expression by redistributing GATA3 away from T(H)2 genes
Hertweck, Arnulf
Vila de Mucha, Maria
Barber, Paul R.
Dagil, Robert
Porter, Hayley
Ramos, Andres
Lord, Graham M.
Jenner, Richard G.
NUCLEIC ACIDS RESEARCH, 2022, 50 (08) : 4557 - 4573
[38] Modulation of chemokine receptor expression and chemotactic responsiveness during differentiation of human naive T cells into Th1 or Th2 cells
Colantonio, L
Recalde, H
Sinigaglia, F
D'Ambrosio, D
EUROPEAN JOURNAL OF IMMUNOLOGY, 2002, 32 (05) : 1264 - 1273
[39] The Ets-1 transcription factor is required for Stat1-mediated T-bet expression and IgG2a class switching in mouse B cells
Hai Vu Nguyen
Mouly, Enguerran
Chemin, Karine
Luinaud, Romain
Despres, Raymonde
Fermand, Jean-Paul
Arnulf, Bertrand
Bories, Jean-Christophe
BLOOD, 2012, 119 (18) : 4174 - 4181
[40] Oral feeding of Lactobacillus bulgaricus N45.10 inhibits the lung inflammation and airway remodeling in murine allergic asthma: Relevance to the Th1/Th2 cytokines and STAT6/T-bet
Anatriello, E.
Cunha, M.
Nogueira, J.
Carvalho, J. L.
Sa, A. K.
Miranda, M.
Castro-Faria-Neto, H.
Keller, A. C.
Aimbire, F.
CELLULAR IMMUNOLOGY, 2019, 341

← 1 2 3 4 5 →