title: Serine protease Per a 10 from Periplaneta americana bias dendritic cells towards type 2 by upregulating CD86 and low IL-12 secretions.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Allergy and Immunology Section, Institute of Genomics and Integrative Biology (CSIR), Delhi, India.
authors.forename: C
authors.initials: C
authors.lastname: Goel
authors.forename: D
authors.initials: D
authors.lastname: Govindaraj
authors.forename: B P
authors.initials: BP
authors.lastname: Singh
authors.forename: A
authors.initials: A
authors.lastname: Farooque
authors.forename: N
authors.initials: N
authors.lastname: Kalra
authors.forename: N
authors.initials: N
authors.lastname: Arora
mesh_terms: D000485:Allergens / Q000276:immunology*; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D051940:B7-2 Antigen / Q000096:biosynthesis* / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D010526:Periplaneta / Q000276:immunology*; D010641:Phenotype; D057057:Serine Proteases / Q000276:immunology*
chemical_list: D000485:Allergens; D051940:B7-2 Antigen; D016207:Cytokines; D018664:Interleukin-12; D057057:Serine Proteases