Gut epithelial IL-27 confers intestinal immunity through the induction of intraepithelial lymphocytes
Open Access
- 23 September 2021
- journal article
- research article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 218 (11)
- https://doi.org/10.1084/jem.20210021
Abstract
IL-27 controls a diverse range of immune responses in many disease settings. Here, we identify intestinal epithelial cells (IECs) as one of the major IL-27 cellular sources in the gut-associated tissue. Unlike IL-27 secreted by innate immune cells, gut epithelial IL-27 is dispensable for T-bet+ regulatory T cell (T reg cell) differentiation or IL-10 induction. Rather, IEC-derived IL-27 specifically promotes a distinct CD8αα+CD4+ intraepithelial lymphocyte (IEL) population that acquires their functional differentiation at the intestinal epithelium. Loss of IL-27 in IECs leads to a selective defect in CD8αα+CD4+ IELs over time. Consequently, mice with IEC-specific IL-27 ablation exhibited elevated pathogen burden during parasitic infection, and this could be rescued by transfer of exogenous CD8αα+CD4+ IELs. Collectively, our data reveal that in addition to its known regulatory properties in preventing immune hyperactivity, gut epithelial IL-27 confers barrier immunity by inducing a specific IEL subset and further suggest that IL-27 produced by different cell types plays distinct roles in maintaining intestinal homeostasis.Keywords
Funding Information
- National Institutes of Health (AI108651, AI127751, AI163813, AI125247)
This publication has 42 references indexed in Scilit:
- Replication and Distribution of Toxoplasma gondii in the Small Intestine after Oral Infection with Tissue CystsInfection and Immunity, 2013
- A Novel Role for Interleukin-27 (IL-27) as Mediator of Intestinal Epithelial Barrier Protection Mediated via Differential Signal Transducer and Activator of Transcription (STAT) Protein Signaling and Induction of Antibacterial and Anti-inflammatory ProteinsOnline Journal of Public Health Informatics, 2012
- The light and dark sides of intestinal intraepithelial lymphocytesNature Reviews Immunology, 2011
- IL-27 promotes T cell–dependent colitis through multiple mechanismsThe Journal of Experimental Medicine, 2010
- Gut Commensal Bacteria Direct a Protective Immune Response against Toxoplasma gondiiCell Host & Microbe, 2009
- Dynamic Imaging of CD8+ T Cells and Dendritic Cells during Infection with Toxoplasma gondiiPLoS Pathogens, 2009
- Effector memory T cell responses are associated with protection of rhesus monkeys from mucosal simian immunodeficiency virus challengeNature Medicine, 2009
- Dynamics of Neutrophil Migration in Lymph Nodes during InfectionImmunity, 2008
- Regulation of IL-27 p28 gene expression in macrophages through MyD88- and interferon-γ–mediated pathwaysThe Journal of Experimental Medicine, 2007
- Interleukin 27 limits autoimmune encephalomyelitis by suppressing the development of interleukin 17–producing T cellsNature Immunology, 2006