Granzyme A Is Required for Regulatory T-Cell Mediated Prevention of Gastrointestinal Graft-versus-Host Disease. 2015

Sarvari Velaga, and Sya N Ukena, and Ulrike Dringenberg, and Christina Alter, and Julian Pardo, and Olivia Kershaw, and Anke Franzke
Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.

In our previous work we could identify defects in human regulatory T cells (Tregs) likely favoring the development of graft-versus-host disease (GvHD) following allogeneic stem cell transplantation (SCT). Treg transcriptome analyses comparing GvHD and immune tolerant patients uncovered regulated gene transcripts highly relevant for Treg cell function. Moreover, granzyme A (GZMA) also showed a significant lower expression at the protein level in Tregs of GvHD patients. GZMA induces cytolysis in a perforin-dependent, FAS-FASL independent manner and represents a cell-contact dependent mechanism for Tregs to control immune responses. We therefore analyzed the functional role of GZMA in a murine standard model for GvHD. For this purpose, adoptively transferred CD4+CD25+ Tregs from gzmA-/- mice were analyzed in comparison to their wild type counterparts for their capability to prevent murine GvHD. GzmA-/- Tregs home efficiently to secondary lymphoid organs and do not show phenotypic alterations with respect to activation and migration properties to inflammatory sites. Whereas gzmA-/- Tregs are highly suppressive in vitro, Tregs require GZMA to rescue hosts from murine GvHD, especially regarding gastrointestinal target organ damage. We herewith identify GZMA as critical effector molecule of human Treg function for gastrointestinal immune response in an experimental GvHD model.

UI MeSH Term Description Entries
D008221 Lymphoid Tissue Specialized tissues that are components of the lymphatic system. They provide fixed locations within the body where a variety of LYMPHOCYTES can form, mature and multiply. The lymphoid tissues are connected by a network of LYMPHATIC VESSELS. Lymphatic Tissue,Lymphatic Tissues,Lymphoid Tissues,Tissue, Lymphatic,Tissue, Lymphoid,Tissues, Lymphatic,Tissues, Lymphoid
D010641 Phenotype The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment. Phenotypes
D002465 Cell Movement The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell. Cell Migration,Locomotion, Cell,Migration, Cell,Motility, Cell,Movement, Cell,Cell Locomotion,Cell Motility,Cell Movements,Movements, Cell
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D005767 Gastrointestinal Diseases Diseases in any segment of the GASTROINTESTINAL TRACT from ESOPHAGUS to RECTUM. Cholera Infantum,Gastrointestinal Disorders,Functional Gastrointestinal Disorders,Gastrointestinal Disorders, Functional,Disease, Gastrointestinal,Diseases, Gastrointestinal,Functional Gastrointestinal Disorder,Gastrointestinal Disease,Gastrointestinal Disorder,Gastrointestinal Disorder, Functional
D006086 Graft vs Host Disease The clinical entity characterized by anorexia, diarrhea, loss of hair, leukopenia, thrombocytopenia, growth retardation, and eventual death brought about by the GRAFT VS HOST REACTION. Graft-Versus-Host Disease,Homologous Wasting Disease,Runt Disease,Graft-vs-Host Disease,Disease, Graft-Versus-Host,Disease, Graft-vs-Host,Disease, Homologous Wasting,Disease, Runt,Diseases, Graft-Versus-Host,Diseases, Graft-vs-Host,Graft Versus Host Disease,Graft-Versus-Host Diseases,Graft-vs-Host Diseases
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015870 Gene Expression The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION. Expression, Gene,Expressions, Gene,Gene Expressions
D016130 Immunophenotyping Process of classifying cells of the immune system based on structural and functional differences. The process is commonly used to analyze and sort T-lymphocytes into subsets based on CD antigens by the technique of flow cytometry. Lymphocyte Immunophenotyping,Lymphocyte Subtyping,Immunologic Subtyping,Immunologic Subtypings,Lymphocyte Phenotyping,Subtyping, Immunologic,Subtypings, Immunologic,Immunophenotyping, Lymphocyte,Immunophenotypings,Immunophenotypings, Lymphocyte,Lymphocyte Immunophenotypings,Lymphocyte Phenotypings,Lymphocyte Subtypings,Phenotyping, Lymphocyte,Phenotypings, Lymphocyte,Subtyping, Lymphocyte,Subtypings, Lymphocyte

Related Publications

Sarvari Velaga, and Sya N Ukena, and Ulrike Dringenberg, and Christina Alter, and Julian Pardo, and Olivia Kershaw, and Anke Franzke
March 2010, Blood,
Sarvari Velaga, and Sya N Ukena, and Ulrike Dringenberg, and Christina Alter, and Julian Pardo, and Olivia Kershaw, and Anke Franzke
January 2016, Journal of immunology research and therapy,
Sarvari Velaga, and Sya N Ukena, and Ulrike Dringenberg, and Christina Alter, and Julian Pardo, and Olivia Kershaw, and Anke Franzke
January 2012, American journal of blood research,
Sarvari Velaga, and Sya N Ukena, and Ulrike Dringenberg, and Christina Alter, and Julian Pardo, and Olivia Kershaw, and Anke Franzke
June 2018, Blood,
Sarvari Velaga, and Sya N Ukena, and Ulrike Dringenberg, and Christina Alter, and Julian Pardo, and Olivia Kershaw, and Anke Franzke
June 2014, [Rinsho ketsueki] The Japanese journal of clinical hematology,
Sarvari Velaga, and Sya N Ukena, and Ulrike Dringenberg, and Christina Alter, and Julian Pardo, and Olivia Kershaw, and Anke Franzke
November 2009, European journal of immunology,
Sarvari Velaga, and Sya N Ukena, and Ulrike Dringenberg, and Christina Alter, and Julian Pardo, and Olivia Kershaw, and Anke Franzke
May 2012, BMC medicine,
Sarvari Velaga, and Sya N Ukena, and Ulrike Dringenberg, and Christina Alter, and Julian Pardo, and Olivia Kershaw, and Anke Franzke
September 2020, JCI insight,
Sarvari Velaga, and Sya N Ukena, and Ulrike Dringenberg, and Christina Alter, and Julian Pardo, and Olivia Kershaw, and Anke Franzke
March 2012, The New England journal of medicine,
Sarvari Velaga, and Sya N Ukena, and Ulrike Dringenberg, and Christina Alter, and Julian Pardo, and Olivia Kershaw, and Anke Franzke
March 2012, The New England journal of medicine,
Copied contents to your clipboard!