STAT-3–independent production of IL-17 by mouse innate-like αβ T cells controls ocular infection

St. Leger et al. identify and examine innate-like αβ T cells that circumvent canonical STAT-3 phosphorylation to produce protective IL-17. These cells can exist in the ocular mucosa and protect the ocular surface from pathogenic Staphylococcus aureus infection.
Appropriate regulation of IL-17 production in the host can mean the difference between effective control of pathogens and uncontrolled inflammation that causes tissue damage. Investigation of conventional CD4+ T cells (Th17 cells) has yielded invaluable insights into IL-17 function and its regulation. More recently, we and others reported production of IL-17 from innate αβ+ T cell populations, which was shown to occur primarily via IL-23R signaling through the transcription factor STAT-3. In our current study, we identify promyelocytic leukemia zinc finger (PLZF)–expressing iNKT, CD4−/CD8+, and CD4−/CD8− (DN) αβ+T cells, which produce IL-17 in response to TCR and IL-1 receptor ligation independently of STAT-3 signaling. Notably, this noncanonical pathway of IL-17 production may be important in mucosal defense and is by itself sufficient to control pathogenic Staphylococcus aureus infection at the ocular surface.
Graphical Abstract