The transcription factors Runx3 and ThPOK cross-regulate acquisition of cytotoxic function by human Th1 lymphocytes.
Yasmina Serroukh,Chunyan Gu-Trantien,Baharak Hooshiar Kashani,Matthieu Defrance,Thien-Phong Vu Manh,Abdulkader Azouz,Aurélie Detavernier,Alice Hoyois,Jishnu Das,Jishnu Das,Martin Bizet,Emeline Pollet,Tressy Tabbuso,Emilie Calonne,Klaas P. J. M. van Gisbergen,Marc Dalod,François Fuks,Stanislas Goriely,Arnaud Marchant +18 more
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This work elucidates the molecular program of human CD4CTX T cells and identifies potential targets for immunotherapy against viral infections and cancer.Abstract:
Cytotoxic CD4 (CD4CTX) T cells are emerging as an important component of antiviral and antitumor immunity, but the molecular basis of their development remains poorly understood. In the context of human cytomegalovirus infection, a significant proportion of CD4 T cells displays cytotoxic functions. We observed that the transcriptional program of these cells was enriched in CD8 T cell lineage genes despite the absence of ThPOK downregulation. We further show that establishment of CD4CTX-specific transcriptional and epigenetic programs occurred in a stepwise fashion along the Th1-differentiation pathway. In vitro, prolonged activation of naive CD4 T cells in presence of Th1 polarizing cytokines led to the acquisition of perforin-dependent cytotoxic activity. This process was dependent on the Th1 transcription factor Runx3 and was limited by the sustained expression of ThPOK. This work elucidates the molecular program of human CD4CTX T cells and identifies potential targets for immunotherapy against viral infections and cancer.read more
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Hobit and Blimp1 instruct a universal transcriptional program of tissue-residency in lymphocytes
Laura K. Mackay,Martina Minnich,Natasja A. M. Kragten,Cyril Seillet,David Freestone,Gabrielle T. Belz,Meinrad Busslinger,Wei Shi,Francis R. Carbone,R. A. W. Van Lier,Axel Kallies,K van Gisbergen +11 more
TL;DR: It is shown that the transcription factor Hobit is specifically up-regulated in Trm cells and, together with related Blimp1, mediates the development of Trms cells in skin, gut, liver, and kidney in mice.
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Discriminating mild from critical COVID-19 by innate and adaptive immune single-cell profiling of bronchoalveolar lavages.
Els Wauters,Pierre Van Mol,Abhishek D. Garg,Sander Jansen,Yannick Van Herck,Lore Vanderbeke,Ayse Bassez,Bram Boeckx,Bert Malengier-Devlies,Anna Timmerman,Thomas Van Brussel,Tina Van Buyten,Rogier Schepers,Elisabeth Heylen,Dieter Dauwe,Christophe Dooms,Jan Gunst,Greet Hermans,Philippe Meersseman,Dries Testelmans,Jonas Yserbyt,Sabine Tejpar,Walter De Wever,Patrick Matthys,Johan Neyts,Joost Wauters,Junbin Qian,Diether Lambrechts +27 more
TL;DR: In this article, the authors used pseudotime inference to build T-cell and monocyte-to-macrophage trajectories and model gene expression changes along them and found that in mild COVID-19, CD8+ resident-memory (TRM) and CD4+ T-helper-17 (TH17) cells undergo active expansion towards the end of the trajectory, and are characterized by good effector functions, while in critical COVID19 they remain more naive.
Journal ArticleDOI
Tumor-specific cytolytic CD4 T cells mediate immunity against human cancer
Amélie Cachot,Mariia Bilous,Mariia Bilous,Yen-Cheng Liu,Xiaokang Li,Margaux Saillard,Mara Cenerenti,Mara Cenerenti,Georg Alexander Rockinger,Tania Wyss,Tania Wyss,Philippe Guillaume,Julien Schmidt,Raphael Genolet,Giuseppe Ercolano,Giuseppe Ercolano,Maria Pia Protti,Walter Reith,Kalliopi Ioannidou,Laurence de Leval,Joseph A. Trapani,George Coukos,Alexandre Harari,Daniel E. Speiser,Alexander Mathis,Alexander Mathis,David Gfeller,David Gfeller,Hatice Altug,Pedro Romero,Camilla Jandus,Camilla Jandus +31 more
TL;DR: In this article, using the peptide-MHCII-multimer technology, the authors confirmed ex vivo the presence of cytolytic tumor-specific CD4 T cells.
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CD4 T Helper Cell Subsets and Related Human Immunological Disorders.
Xiaoliang Zhu,Jinfang Zhu +1 more
TL;DR: The differentiation and functions of each CD4 T helper cell subset are discussed in the context of ILCs and human diseases associated with the dysregulation of these lymphocyte subsets particularly caused by monogenic mutations.
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Single-cell transcriptomic analysis of allergen-specific T cells in allergy and asthma
Grégory Seumois,Ciro Ramírez-Suástegui,Benjamin J Schmiedel,Shu Liang,Bjoern Peters,Bjoern Peters,Alessandro Sette,Alessandro Sette,Pandurangan Vijayanand,Pandurangan Vijayanand,Pandurangan Vijayanand +10 more
TL;DR: It is suggested that the THIFNR and TregIFNR subsets may dampen allergic responses, which may help explain why only some people develop TH2 responses to nearly ubiquitous allergens.
References
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Journal ArticleDOI
Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles
Aravind Subramanian,Pablo Tamayo,Vamsi K. Mootha,Sayan Mukherjee,Benjamin L. Ebert,Michael A. Gillette,Amanda G. Paulovich,Scott L. Pomeroy,Todd R. Golub,Eric S. Lander,Jill P. Mesirov +10 more
TL;DR: The Gene Set Enrichment Analysis (GSEA) method as discussed by the authors focuses on gene sets, that is, groups of genes that share common biological function, chromosomal location, or regulation.
Journal ArticleDOI
Pvclust: an R package for assessing the uncertainty in hierarchical clustering
TL;DR: Pvclust is an add-on package for a statistical software R to assess the uncertainty in hierarchical cluster analysis to perform the bootstrap analysis of clustering, which has been popular in phylogenetic analysis.
Journal ArticleDOI
lumi: a pipeline for processing Illumina microarray
Pan Du,Warren A. Kibbe,Simon Lin +2 more
TL;DR: The lumi package as discussed by the authors is a Bioconductor package designed to process the Illumina microarray data, which includes data input, quality control, variance stabilization, normalization and gene annotation portions.
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Memory CD8+ T cells vary in differentiation phenotype in different persistent virus infections.
Victor Appay,P. Rod Dunbar,Margaret F. C. Callan,Paul Klenerman,Geraldine M. Gillespie,Laura Papagno,Graham S. Ogg,Abigail S. King,Franziska Lechner,Celsa A. Spina,Susan J. Little,Diane V. Havlir,Douglas D. Richman,Norbert H. Gruener,Gerd R. Pape,Anele Waters,Philippa Easterbrook,Mariolina Salio,Vincenzo Cerundolo,Andrew J. McMichael,Sarah Rowland-Jones +20 more
TL;DR: There are significant enrichments at different stages of cellular differentiation in the chronic phase of persistent infection according to the viral specificity, which suggests that distinct memory T-cell populations are established in different virus infections.
Journal ArticleDOI
Flexible programs of chemokine receptor expression on human polarized T helper 1 and 2 lymphocytes.
TL;DR: It is demonstrated that chemokine receptors are markers of naive and polarized T cell subsets and suggested that flexible programs of chemokin receptor gene expression may control tissue-specific migration of effector T cells.
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