[en] Parasitic helminths induce the production of interleukin-4 (IL-4), which causes the expansion of virtual memory CD8+ T cells (TVM cells), a cell subset that contributes to the control of coinfection with intracellular pathogens. However, the mechanisms regulating IL-4-dependent TVM cell activation and expansion remain ill defined. Here, we used single-cell RNA sequencing of CD8+ T cells to identify pathways that control IL-4-dependent TVM cell responses. Gene signature analysis of CD8+ T cells identified a cell cluster marked by CD22, a canonical regulator of B cell activation, as a selective surface marker of IL-4-induced TVM cells. CD22+ TVM cells were enriched for interferon-γ and granzyme A and retained a diverse TCR repertoire while enriched in self-reactive CDR3 sequences. CD22 intrinsically regulated the IL-4-induced CD8+ T cell effector program, resulting in reduced responsiveness of CD22+ TVM cells and regulatory functions to infection and inflammation. Thus, helminth-induced IL-4 drives the expansion and activation of TVM cells that is counterinhibited by CD22.
Research Center/Unit :
FARAH. Santé publique vétérinaire - ULiège
Disciplines :
Immunology & infectious disease
Author, co-author :
Yang, Bin ; Université de Liège - ULiège > Fundamental and Applied Research for Animals and Health (FARAH) > FARAH: Santé publique vétérinaire
Piedfort, Ophélie ; Université de Liège - ULiège > Département des maladies infectieuses et parasitaires (DMI)
Sanchez-Sanchez, Guillem ; Department of Pharmacotherapy and Pharmaceutics, Université Libre de Bruxelles (ULB), Brussels, Belgium ; Institute for Medical Immunology (IMI), ULB, Gosselies, Belgium ; ULB Center for Research in Immunology (U-CRI), Gosselies, Belgium
Lavergne, Arnaud ; Université de Liège - ULiège > Département de gestion vétérinaire des Ressources Animales (DRA)
Gong, Meijiao ; Université de Liège - ULiège > Fundamental and Applied Research for Animals and Health (FARAH)
Peng, Garrie ; Department of Microbiology and Immunology, Meakins-Christie Laboratories, Research Institute of McGill University Health Centre, Montreal, Quebec, Canada ; McGill Interdisciplinary Initiative in Infection and Immunity, Montreal, Quebec, Canada ; McGill Centre for Microbiome Research, Montreal, Quebec, Canada
Madrigal, Ariel ; Department of Human Genetics, McGill University, Montreal, QC H3A 0C7, Canada ; McGill Genome Centre, Dahdaleh Institute of Genomic Medicine, Montreal, QC H3A 0G1, Canada
Petrellis, Georgios ; Université de Liège - ULiège > Fundamental and Applied Research for Animals and Health (FARAH) > FARAH: Santé publique vétérinaire
Katsandegwaza, Brunette ; Université de Liège - ULiège > Fundamental and Applied Research for Animals and Health (FARAH) > FARAH: Santé publique vétérinaire
Rodriguez, Lucia Rodriguez ; Department of Infectious and Parasitic Diseases, Faculty of Veterinary Medicine - FARAH, University of Liège, Liège, Belgium
Balthazar, Alexis ; Université de Liège - ULiège > Département des maladies infectieuses et parasitaires (DMI) > Vaccinologie vétérinaire
Meyer, Sarah J ; Division of Genetics, Department of Biology, University of Erlangen, 91058 Erlangen, Germany
Van Isterdael, Gert ; VIB Flow Core, VIB Center for Inflammation Research, Ghent, Belgium ; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium
Van Duyse, Julie ; VIB Flow Core, VIB Center for Inflammation Research, Ghent, Belgium ; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium
Andris, Fabienne; Institute for Medical Immunology (IMI), ULB, Gosselies, Belgium
Bai, Qiang ; Université de Liège - ULiège > Département des sciences fonctionnelles (DSF) ; PhyMedExp, INSERM U1046, University of Montpellier, Montpellier, France
Marichal, Thomas ; Université de Liège - ULiège > GIGA > GIGA Immunobiology - Immunophysiology ; Walloon Excellence in Life Sciences and Biotechnology (WELBIO) Department, WEL Research Institute, Wavre, Belgium
Machiels, Bénédicte ; Université de Liège - ULiège > Département des maladies infectieuses et parasitaires (DMI) > Vaccinologie vétérinaire ; Walloon Excellence in Life Sciences and Biotechnology (WELBIO) Department, WEL Research Institute, Wavre, Belgium
Nitschke, Lars; Division of Genetics, Department of Biology, University of Erlangen, 91058 Erlangen, Germany
Najafabadi, Hamed S ; Department of Human Genetics, McGill University, Montreal, QC H3A 0C7, Canada ; McGill Genome Centre, Dahdaleh Institute of Genomic Medicine, Montreal, QC H3A 0G1, Canada
King, Irah L ; Department of Microbiology and Immunology, Meakins-Christie Laboratories, Research Institute of McGill University Health Centre, Montreal, Quebec, Canada ; McGill Interdisciplinary Initiative in Infection and Immunity, Montreal, Quebec, Canada ; McGill Centre for Microbiome Research, Montreal, Quebec, Canada
Vermijlen, David ; Department of Pharmacotherapy and Pharmaceutics, Université Libre de Bruxelles (ULB), Brussels, Belgium ; Institute for Medical Immunology (IMI), ULB, Gosselies, Belgium ; ULB Center for Research in Immunology (U-CRI), Gosselies, Belgium ; Walloon Excellence in Life Sciences and Biotechnology (WELBIO) Department, WEL Research Institute, Wavre, Belgium
Dewals, Benjamin G ; Université de Liège - ULiège > Département des maladies infectieuses et parasitaires (DMI) > Immunologie vétérinaire ; Walloon Excellence in Life Sciences and Biotechnology (WELBIO) Department, WEL Research Institute, Wavre, Belgium
F.R.S.-FNRS - Fonds de la Recherche Scientifique ULiège FSR - Université de Liège. Fonds spéciaux pour la recherche WELBIO - Walloon Excellence in Life Sciences and Biotechnology
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