6533b852fe1ef96bd12aac63

RESEARCH PRODUCT

Intrinsic TNFR2 signaling in T regulatory cells provides protection in CNS autoimmunity

Ilgiz A. MufazalovIlgiz A. MufazalovAnna KuchmiyAnna KuchmiyM. S. DrutskayaM. S. DrutskayaAndrey KruglovDavid AndruszewskiSergei A. NedospasovVioletta S. GogolevaVioletta S. GogolevaJosefine DunstMarius SchwabenlandKamar-sulu N. AtretkhanyAri WaismanMarco PrinzDenise L. Faustman

subject

Central Nervous System0301 basic medicineEncephalomyelitis Autoimmune ExperimentalT regulatory cellsmedicine.medical_treatmentAutoimmunitychemical and pharmacologic phenomenaBiologymedicine.disease_causeT-Lymphocytes RegulatoryneuroinflammationAutoimmunityMice03 medical and health sciencesImmunology and Inflammation0302 clinical medicineImmune systemmedicineAnimalsHumansReceptors Tumor Necrosis Factor Type IIIL-2 receptorCells CulturedNeuroinflammationMice KnockoutAutoimmune diseaseMultidisciplinaryEAETumor Necrosis Factor-alphaExperimental autoimmune encephalomyelitisFOXP3hemic and immune systemsBiological Sciencesmedicine.diseaseTNF/TNFR2Mice Inbred C57BLDisease Models Animalhumanized mice030104 developmental biologyCytokineGene Expression RegulationImmunology030215 immunology

description

Significance In spite of TNF involvement in the pathogenesis of multiple sclerosis (MS), systemic TNF neutralization in MS patients was not successful. One of the possible reasons is that TNF possesses both pathogenic and protective features that may be related to TNFR1 versus TNFR2 receptor engagement. This study uncovers one of such protective functions of TNF mediated by intrinsic TNFR2 signaling in Treg cells. In mice bearing humanized TNF and TNFR2 genetic loci, TNFR2 ablation restricted to Treg cells led to reduced capacity to control Th17 cell responses, exacerbated experimental autoimmune encephalomyelitis (EAE) development, and affected the maintenance of Treg cells. These findings provide support for the emerging role of TNFR2 signaling in autoimmunity, as demonstrated here in mice with conditional inactivation of TNFR2.

yearjournalcountryeditionlanguage
2018-11-01Proceedings of the National Academy of Sciences
https://doi.org/10.1073/pnas.1807499115