Background
IL-13 is a central mediator of airway responsiveness and mucus expression in patients with allergic airway inflammation, and IL-13 is currently a therapeutic target for asthma. However, little is known about how IL-13 regulates human CD4
+ T-cell lineages because IL-13 receptor (IL-13R) &#
x3b1;1, a subunit of IL-13R, has not previously been reported to exist on human T cells.
Objective
We sought to determine whether human CD4+ TH17 cells express IL-13Rα1 and whether IL-13 regulates TH17 cytokine production.
Methods
Naive human CD4+ cells were isolated from whole blood, activated with anti-CD3 and anti-CD28, and polarized to TH1, TH2, TH17, or induced regulatory T cells in the presence of IL-13 (0-10 ng/mL). Cell supernatants, total RNA, or total protein was examined 4 days after TH17 polarization.
Results
TH17 cells, but not TH0, TH1, TH2, or induced regulatory T cells, expressed IL-13Rα1. IL-13 attenuated IL-17A production, as well as expression of retinoic acid–related orphan receptor, runt-related transcription factor-1, and interferon regulatory factor 4 in TH17-polarized cells. IL-13 neither inhibited IFN-γ production from TH1 cells nor inhibited IL-4 production from TH2 cells. Furthermore, attenuation of IL-17A production only occurred when IL-13 was present within 24 hours of T-cell activation or at the time of restimulation.
Conclusions
IL-13Rα1 is expressed on human CD4+ TH17 cells, and IL-13 attenuates IL-17A production at polarization and restimulation. Although IL-13 is an attractive therapeutic target for decreasing symptoms associated with asthma, these results suggest that therapies inhibiting IL-13 production could have adverse side effects by increasing IL-17A production.
