0000000001145151

AUTHOR

Fred Lühder

showing 3 related works from this author

Tyrphostin AG126 exerts neuroprotection in CNS inflammation by a dual mechanism

2015

The putative protein tyrosine kinase (PTK) inhibitor tyrphostin AG126 has proven beneficial in various models of inflammatory disease. Yet molecular targets and cellular mechanisms remained enigmatic. We demonstrate here that AG126 treatment has beneficial effects in experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis. AG126 alleviates the clinical symptoms, diminishes encephalitogenic Th17 differentiation, reduces inflammatory CNS infiltration as well as microglia activation and attenuates myelin damage. We show that AG126 directly inhibits Bruton's tyrosine kinase (BTK), a PTK associated with B cell receptor and Toll-like receptor (TLR) signaling. However, BTK …

MicrogliabiologyExperimental autoimmune encephalomyelitisB-cell receptorInflammationmedicine.diseaseNeuroprotectionProinflammatory cytokineCell biologyCellular and Molecular Neurosciencemedicine.anatomical_structureNeurologyImmunologymedicinebiology.proteinBruton's tyrosine kinasemedicine.symptomTyrosine kinaseGlia
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Interruption of CD28-mediated costimulation during allergen challenge protects mice from allergic airway disease

2012

Background Allergic asthma is a T H 2-promoted hyperreactivity with an immediate, IgE, and mast cell–dependent response followed by eosinophil-dominated inflammation and airway obstruction. Objective Because costimulation by CD28 is essential for T H 2 but not T H 1 responses, we investigated the effect of selective interference with this pathway in mice using the models of ovalbumin and house dust mite–induced airway inflammation. Methods To study the role of CD28 in the effector phase of allergic airway inflammation, we developed an inducibly CD28-deleting mouse strain or alternatively used a CD28 ligand-binding site–specific mouse anti-mouse mAb blocking CD28 engagement. Results We show …

Allergic asthmaLymphocyte ActivationImmunoglobulin Emedicine.disease_causeT-Lymphocytes RegulatoryMice0302 clinical medicineAirway resistanceAllergenImmunology and AllergySensitizationMice Inbred BALB C0303 health sciencesbiologyAntibodies Monoclonalovalbuminrespiratory system3. Good healthmedicine.anatomical_structurecostimulationconditional CD28 knockout miceFemalemedicine.symptomImmunologyInflammation03 medical and health sciencesTh2 CellsCD28 AntigensRespiratory HypersensitivitymedicineAnimalsHumansAntigens DermatophagoidesLymphocyte CountAntibodies Blocking030304 developmental biologyHouse dust miteCD28-specific mAbbusiness.industryReceptor Cross-TalkAirway obstructionmedicine.diseasebiology.organism_classificationMice Mutant Strainsrespiratory tract diseasesDisease Models AnimalCTLA-4Immunologybiology.proteinbusiness030215 immunology
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Protection of Mice from Acute Graft-versus-Host Disease Requires CD28 Co-stimulation on Donor CD4+ Foxp3+ Regulatory T Cells

2017

Acute graft-versus-host disease (aGvHD) is a major cause of morbidity and mortality after allogeneic hematopoietic stem cell plus T cell transplantation (allo-HSCT). In this study, we investigated the requirement for CD28 co-stimulation of donor CD4\(^{+}\) conventional (CD4\(^{+}\)CD25\(^{-}\)Foxp3\(^{-}\), Tconv) and regulatory (CD4\(^{+}\)CD25\(^{+}\)Foxp3\(^{+}\), Treg) T cells in aGvHD using tamoxifen-inducible CD28 knockout (iCD28KO) or wild-type (wt) littermates as donors of CD4\(^{+}\) Tconv and Treg. In the highly inflammatory C57BL/6 into BALB/c allo-HSCT transplantation model, CD28 depletion on donor CD4\(^{+}\) Tconv reduced clinical signs of aGvHD, but did not significantly pro…

lcsh:Immunologic diseases. AllergyCD28acute graft-versus-host diseaseImmunologyco-stimulationhemic and immune systemschemical and pharmacologic phenomenainducible deletionregulatory T cellssurgical procedures operativeimmune system diseaseshemic and lymphatic diseasesImmunology and Allergyddc:610lcsh:RC581-607Frontiers in Immunology
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