title: Protease activity of Per a 10 potentiates Th2 polarization by increasing IL-23 and OX40L.
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.
authors.affiliation: Allergy and Immunology section, CSIR-Institute of Genomics and Integrative Biology, New Delhi, India.|Academy of Scientific and Innovative Research (AcSIR), CSIR-IGIB Campus, New Delhi, India.
authors.forename: Komal
authors.initials: K
authors.lastname: Agrawal
authors.affiliation: Allergy and Immunology section, CSIR-Institute of Genomics and Integrative Biology, New Delhi, India.
authors.forename: Sagar L
authors.initials: SL
authors.lastname: Kale
authors.affiliation: Allergy and Immunology section, CSIR-Institute of Genomics and Integrative Biology, New Delhi, India.|Academy of Scientific and Innovative Research (AcSIR), CSIR-IGIB Campus, New Delhi, India.
authors.forename: Naveen
authors.initials: N
authors.lastname: Arora
mesh_terms: D000281:Administration, Intranasal; D000485:Allergens / Q000494:pharmacology*; D000818:Animals; D019013:CD40 Antigens / Q000235:genetics; D016764:Cell Polarity; D005260:Female; D053765:Interleukin-12 Subunit p35 / Q000032:analysis / Q000378:metabolism; D053759:Interleukin-23 / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D053278:OX40 Ligand / Q000235:genetics*; D010526:Periplaneta / Q000276:immunology*; D057057:Serine Proteases / Q000494:pharmacology*; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D000485:Allergens; D019013:CD40 Antigens; D053765:Interleukin-12 Subunit p35; D053759:Interleukin-23; D053278:OX40 Ligand; D057057:Serine Proteases
keywords: CD40; Cytokines; Dendritic cell; OX40L; Protease allergen