IL-13-producing Th1 and Th17 cells characterize adaptive responses to both self and foreign antigens.
In helper T cells, IL-13 is traditionally considered a Th2-type cytokine that is coexpressed with IL-4. Using mouse models of immunization and autoimmunity, we demonstrate that IL-13 is frequently uncoupled from IL-4, and that it can be produced by both IFN-γ(+) Th1 cells and IL-17(+) Th17 cells. We report that these IL-13-producing Th1 and Th17 cells are distinct from classical IL-4(+) Th2 cells and that they are relatively common, appearing in the context of both protective and pathogenic T-cell responses. We also demonstrate that IL-13 and Th2-type cytokines can have important consequences in Th1- and Th17-dominated settings, such as lymphopenia-induced autoimmune disease, where they can be either pro- or anti-inflammatory, depending on whether they act on innate or adaptive immune cells. Taken together, our studies indicate that IL-13 production is more widespread than previously appreciated and that blocking this cytokine may have therapeutic benefits even in settings where traditional IL-4-driven Th2-type responses are not evident.
Department of Pathology, University of California San Francisco, San Francisco, CA, USA.
Eugenio
E
Gallo
Shoshana
S
Katzman
Alejandro V
AV
Villarino
D000818:Animals; D000941:Antigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology; D018793:Interleukin-13 / Q000096:biosynthesis* / Q000276:immunology*; D020381:Interleukin-17 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology
D000941:Antigens; D018793:Interleukin-13; D020381:Interleukin-17; D015847:Interleukin-4; D007371:Interferon-gamma