We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Serine protease Per a 10 from Periplaneta americana bias dendritic cells towards type 2 by upregulating CD86 and low IL-12 secretions.
- Authors
Goel, C.; Govindaraj, D.; Singh, B. P.; Farooque, A.; Kalra, N.; Arora, N.
- Abstract
Summary Background Serine protease activity of Per a 10 from Periplaneta americana induces airway inflammation and systemic Th2 response towards self and bystander allergen. Objective In the present study the effect of proteolytic activity of Per a 10 allergen on dendritic cells ( DCs) polarization and consequent T cell response was investigated. Methods Non-atopic subjects with no family history of asthma/allergy were recruited for the study. CD14+ peripheral blood monocytes were purified, differentiated to immature DCs and stimulated with proteolytically active/inactivated native or recombinant Per a 10. DCs phenotype was analysed with flow cytometry and antigen presenting function assessed by co-culturing with autologous CD4+ T cells. Cytokine levels were determined using ELISA. Results Immature DCs differentiated into mature CD14- CD83+ HLA- DR+ cells after incubating with proteolytically active/inactivated or recombinant Per a 10. Proteolytically active Per a 10 induced significant CD86 up-regulation on DCs compared to inactivated or recombinant Per a 10 lacking enzymatic activity. Proteolytic activity of Per a 10 showed dose-dependent effect on expression of CD80, CD86, CD83, CD1a and HLA- DR. However, no significant differences were observed phenotypically in active or inactive forms except for CD86. Active Per a 10 stimulated DCs secreted significantly low IL-12 ( P < 0.01) and high IL-6, compared to inactive forms of Per a 10. Naive CD4+ T cells primed with active Per a 10 pulsed DCs also secreted significantly less IL-12 ( P < 0.01) and high IL-4, IL-5 plus IL-6 ( P < 0.01); in contrast to DCs pulsed with inactivated or recombinant Per a 10. Conclusion and clinical relevance Proteolytic activity of Per a 10 modulates DCs towards type 2 by CD86 up-regulation, high IL-6 and reduced IL-12 secretions. Proteolytically inactive Per a 10 can be further explored for immunotherapy.
- Subjects
SERINE proteinases; AMERICAN cockroach; DENDRITIC cells; TH2 cells; MONOCYTES; PHENOTYPES; FLOW cytometry; CYTOKINES
- Publication
Clinical & Experimental Allergy, 2012, Vol 42, Issue 3, p412
- ISSN
0954-7894
- Publication type
Article
- DOI
10.1111/j.1365-2222.2011.03937.x