ena-STUDY-MHH-30-03-2015-17:26:51:165-119
Interferon-lambda and interleukin-22 cooperate for the induction of interferon-stimulated genes and control of rotavirus infection
The epithelium is the major entry point for many viruses but the processes protecting barrier surfaces against viral infections are incompletely understood. We identify interleukin (IL)-22 produced by group 3 innate lymphoid cells (ILC3s) as an amplifier of interferon (IFN)-lambda signaling, a synergism required to curtail replication of rotavirus, the leading cause of childhood gastroenteritis. Cooperation between IL-22 and IFN-lambda receptors, both of which are preferentially expressed by intestinal epithelial cells, was required for optimal STAT1 transcription factor activation and expression of interferon-stimulated genes. This data suggests that epithelial cells are protected against virus replication by co-opting two evolutionarily related cytokine networks. These data may inform the design of novel immunotherapies of virus infections that are sensitive to IFNs.
The epithelium is the major entry point for many viruses but the processes protecting barrier surfaces against viral infections are incompletely understood. We identify interleukin (IL)-22 produced by group 3 innate lymphoid cells (ILC3s) as an amplifier of interferon (IFN)-lambda signaling, a synergism required to curtail replication of rotavirus, the leading cause of childhood gastroenteritis. Cooperation between IL-22 and IFN-lambda receptors, both of which are preferentially expressed by intestinal epithelial cells, was required for optimal STAT1 transcription factor activation and expression of interferon-stimulated genes. This data suggests that epithelial cells are protected against virus replication by co-opting two evolutionarily related cytokine networks. These data may inform the design of novel immunotherapies of virus infections that are sensitive to IFNs.