Publisher： John Wiley & Sons Inc
E-ISSN： 1521-4141|45|12|3375-3385
ISSN： 0014-2980
Source： EUROPEAN JOURNAL OF IMMUNOLOGY, Vol.45, Iss.12, 2015-12, pp. : 3375-3385
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Abstract
Proteases are implicated in exacerbation of allergic diseases. In this study, the role of proteolytic activity of Per a 10 was evaluated on Th2 polarization. Intranasal administration of Per a 10 in mice led to allergic airway inflammation as seen by higher IgE levels, cellular infiltration, IL‐17A, and Th2 cytokines, whereas, inactive (Δ)Per a 10 showed attenuated response. There was an increased OX40L expression on lung and lymph node dendritic cells in Per a 10 immunized group and on Per a 10 stimulated BMDCs. Reduction in CD40 expression without any change at transcript level in lungs of Per a 10 immunized mice suggested CD40 cleavage. BMDCs pulsed with Per a 10 showed reduced CD40 expression with lower IL‐12p70 secretion as compared to heat inactivated Per a 10. IL‐23, TNF‐α, and IL‐6 levels were significantly higher in Per a 10 stimulated BMDCs supernatant. In DC‐T cell coculture studies, Per a 10 pulsed BMDCs showed higher levels of IL‐4 and IL‐13 that were reduced on blocking of either IL‐23 or OX40L. In conclusion, the data suggests a critical role of protease activity of Per a 10 in promoting Th2 polarization by increasing IL‐23 secretion and OX40L expression on dendritic cells.
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