0000000000021547

AUTHOR

Sebastian Hirth

showing 3 related works from this author

RORgamma-expressing Th17 cells induce murine chronic intestinal inflammation via redundant effects of IL-17A and IL-17F.

2008

Background and Aims IL-17–producing CD4 + T-helper cells (Th17) contribute to chronic autoimmune inflammation in the brain, and levels of Th17-derived cytokines increase in patients with colitis, suggesting a role in pathogenesis. We analyzed the roles of Th17 cells and the transcription factor retinoic acid receptor-related organ receptor (ROR)γ, which regulates Th17 differentiation, in chronic intestinal inflammation. Methods Using an adoptive transfer model of colitis, we compared the colitogenic potential of wild-type, interleukin-17A (IL-17A)–, IL-17F–, IL-22–, and RORγ-deficient CD4 + CD25 − T cells in RAG1-null mice. Results Adoptive transfer of IL-17A–, IL-17F–, or IL-22–deficient T…

Adoptive cell transferNeutrophilsReceptors Retinoic Acidmedicine.medical_treatmentBiologyInflammatory bowel diseasePathogenesisMiceInterferonCell MovementmedicineAnimalsIL-2 receptorColitisCells CulturedReceptors Thyroid HormoneHepatologyInterleukinsInterleukin-17GastroenterologyDendritic CellsT-Lymphocytes Helper-InducerNuclear Receptor Subfamily 1 Group F Member 3medicine.diseaseColitisAdoptive TransferMice Inbred C57BLCytokineImmunologyChronic Diseasebiology.proteinCytokinesAntibodymedicine.drugGastroenterology
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STAT3 links IL-22 signaling in intestinal epithelial cells to mucosal wound healing.

2009

Signal transducer and activator of transcription (STAT) 3 is a pleiotropic transcription factor with important functions in cytokine signaling in a variety of tissues. However, the role of STAT3 in the intestinal epithelium is not well understood. We demonstrate that development of colonic inflammation is associated with the induction of STAT3 activity in intestinal epithelial cells (IECs). Studies in genetically engineered mice showed that epithelial STAT3 activation in dextran sodium sulfate colitis is dependent on interleukin (IL)-22 rather than IL-6. IL-22 was secreted by colonic CD11c+ cells in response to Toll-like receptor stimulation. Conditional knockout mice with an IEC-specific d…

STAT3 Transcription FactorAnimals; Colitis/chemically induced; Colitis/immunology; Dextran Sulfate/pharmacology; Epithelial Cells/cytology; Epithelial Cells/physiology; Gene Expression Profiling; Inflammation/immunology; Inflammation/pathology; Interleukin-6/genetics; Interleukin-6/immunology; Interleukins/genetics; Interleukins/immunology; Intestinal Mucosa/cytology; Intestinal Mucosa/pathology; Mice; Mice Inbred C57BL; Mice Knockout; Oligonucleotide Array Sequence Analysis; STAT3 Transcription Factor/genetics; STAT3 Transcription Factor/metabolism; Signal Transduction/physiology; Wound HealingImmunologyInterleukin 22Mice03 medical and health sciences0302 clinical medicineIntestinal mucosaConditional gene knockoutImmunology and AllergyAnimalsIntestinal MucosaSTAT3Oligonucleotide Array Sequence Analysis030304 developmental biologyInflammationMice KnockoutWound Healing0303 health sciencesbiologyInterleukin-6Gene Expression ProfilingInterleukinsDextran SulfateBrief Definitive ReportEpithelial CellsCell BiologySTAT3 Transcription FactorColitisIntestinal epithelium3. Good healthMice Inbred C57BLbiology.proteinCancer researchSTAT proteinWound healingSignal Transduction030215 immunology
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Externalized decondensed neutrophil chromatin occludes pancreatic ducts and drives pancreatitis

2016

Ductal occlusion has been postulated to precipitate focal pancreatic inflammation, while the nature of the primary occluding agents has remained elusive. Neutrophils make use of histone citrullination by peptidyl arginine deiminase-4 (PADI4) in contact to particulate agents to extrude decondensed chromatin as neutrophil extracellular traps (NETs). In high cellular density, NETs form macroscopically visible aggregates. Here we show that such aggregates form inside pancreatic ducts in humans and mice occluding pancreatic ducts and thereby driving pancreatic inflammation. Experimental models indicate that PADI4 is critical for intraductal aggregate formation and that PADI4-deficiency abrogates…

0301 basic medicineExtracellular TrapsHydrolasesNeutrophilsScienceGeneral Physics and AstronomyBiologyExtracellular TrapsArticleGeneral Biochemistry Genetics and Molecular BiologyMice03 medical and health sciencesPancreatic JuiceProtein-Arginine Deiminase Type 4medicineAnimalsHumansPancreasCeruletideMultidisciplinaryReverse Transcriptase Polymerase Chain ReactionQInterleukin-17Pancreatic DuctsGeneral ChemistryNeutrophil extracellular trapsFlow Cytometrymedicine.diseaseImmunohistochemistryChromatinCell biologyChromatinDisease Models AnimalHistone citrullination030104 developmental biologymedicine.anatomical_structurePancreatitisChronic DiseasePancreatic juiceImmunologyProtein-Arginine DeiminasesCytokinesPancreatitisPancreasCeruletideNature Communications
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