title: Monocyte-derived dendritic cells exposed to Der p 1 allergen enhance the recruitment of Th2 cells: major involvement of the chemokines TARC/CCL17 and MDC/CCL22.
abstract: Dendritic cells (DC) are potent antigen - presenting cells that can orientate the immune response towards a Th1 or a Th2 type. DC produce chemokines that are involved in the recruitment of either Th1 cells, such as IP10 (CXCL10), Th2 cells such as TARC (CCL17) and MDC (CCL22), or non-polarized T cells such as RANTES (CCL5) and MIP-lalpha (CCL3). We investigated whether monocyte-derived DC (MD-DC) generated from healthy donors or from patients sensitive to Dermatophagoides pteronyssinus (Dpt) and exposed to the cysteine-protease Der p 1(allergen of Dpt), could upregulate the expression of chemokines involved in type 1 or type 2 T cell recruitment. MD-DC were pulsed with either Der p 1 or with LPS as the control and the chemokines produced were evaluated using ELISA and chemotaxis assays. Der p 1-pulsed DC from allergic patients showed increased TARC (CCL17) and MDC (CCL22) production without modifying IP-10 (CXCL10) release. Der p 1-pulsed DC from healthy donors showed only increased IP-10 (CXCL10) secretion. RANTES (CCL5) and MIP-lalpha (CCL3) production were similarly increased when DC were from healthy or allergic donors. The selective Th2 clone recruitment activity of supernatants from Der p 1-pulsed DC of allergic patients was inhibited by anti-TARC (CCL17) and anti-MDC (CCL22) neutralizing Abs. By using anti-IP10 (CXCL10) blocking Abs, supernatants of Der p 1-pulsed DC from healthy donors were shown to be involved in the recruitment of Th1 cells. These results suggest that in allergic patients exposed to house dust mites, DC may favour the exacerbation of the Th2 response via the increase in type 2 chemokine production.
authors.affiliation: INSERM U416, IFR 17, Institut Pasteur de Lille, France.
authors.forename: Hamida
authors.initials: H
authors.lastname: Hammad
authors.forename: Hermelijn H
authors.initials: HH
authors.lastname: Smits
authors.forename: Céline
authors.initials: C
authors.lastname: Ratajczak
authors.forename: Asokananthan
authors.initials: A
authors.lastname: Nithiananthan
authors.forename: Eddy A
authors.initials: EA
authors.lastname: Wierenga
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Stewart
authors.forename: Alain
authors.initials: A
authors.lastname: Jacquet
authors.forename: Andre-Bernard
authors.initials: AB
authors.lastname: Tonnel
authors.forename: Joël
authors.initials: J
authors.lastname: Pestel
mesh_terms: D039741:Antigens, Dermatophagoides / Q000276:immunology*; D060829:Arthropod Proteins; D054414:Chemokine CCL17; D054422:Chemokine CCL22; D019742:Chemokines, CC / Q000378:metabolism; D003546:Cysteine Endopeptidases; D003713:Dendritic Cells / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism
chemical_list: D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; C106230:CCL17 protein, human; C515482:CCL22 protein, human; D054414:Chemokine CCL17; D054422:Chemokine CCL22; D019742:Chemokines, CC; D003546:Cysteine Endopeptidases; C451162:Dermatophagoides pteronyssinus antigen p 1