6533b858fe1ef96bd12b62e6

RESEARCH PRODUCT

Interferon-λ and interleukin 22 act synergistically for the induction of interferon-stimulated genes and control of rotavirus infection.

Bernhard RyffelBernhard RyffelBernhard RyffelKonrad GronkePedro P. HernandezPedro P. HernandezAndreas DiefenbachFabian GuendelInes YangJean-christophe RenauldPeter StaeheliVera SchwierzeckNam NguyenLaure DumoutierSebastian SuerbaumChristoph HölscherTanel Mahlakõiv

subject

ImmunologyImmunoblottingMolecular Sequence DataGene ExpressionMice Transgenicmedicine.disease_causeRotavirus InfectionsCell LineMadin Darby Canine Kidney CellsInterleukin 22DogsInterferonRotavirusChlorocebus aethiopsmedicineImmunology and AllergyAnimalsHumansSTAT1Intestinal MucosaReceptors CytokineVero CellsMice KnockoutbiologyReverse Transcriptase Polymerase Chain ReactionInterleukinsInnate lymphoid cellInterleukinDrug SynergismEpithelial CellsVirology3. Good healthIntestinesMice Inbred C57BLSTAT1 Transcription FactorViral replicationImmunologybiology.proteinVero cellCytokinesCaco-2 CellsHT29 Cellsmedicine.drug

description

The epithelium is the main entry point for many viruses, but the processes that protect barrier surfaces against viral infections are incompletely understood. Here we identified interleukin 22 (IL-22) produced by innate lymphoid cell group 3 (ILC3) as an amplifier of signaling via interferon-λ (IFN-λ), a synergism needed to curtail the replication of rotavirus, the leading cause of childhood gastroenteritis. Cooperation between the receptor for IL-22 and the receptor for IFN-λ, both of which were 'preferentially' expressed by intestinal epithelial cells (IECs), was required for optimal activation of the transcription factor STAT1 and expression of interferon-stimulated genes (ISGs). These data suggested that epithelial cells are protected against viral replication by co-option of two evolutionarily related cytokine networks. These data may inform the design of novel immunotherapy for viral infections that are sensitive to interferons.

yearjournalcountryeditionlanguage
2015-01-26Nature immunology
10.1038/ni.3180https://pubmed.ncbi.nlm.nih.gov/26052097