Conventional and Monocyte-Derived CD11b+ Dendritic Cells Initiate and Maintain T Helper 2 Cell-Mediated Immunity to House Dust Mite Allergen

• Published in: Immunity (Cambridge, Mass.) Vol. 38; no. 2; pp. 322 - 335
• Main Authors: Plantinga, Maud, Guilliams, Martin, Vanheerswynghels, Manon, Deswarte, Kim, Branco-Madeira, Filipe, Toussaint, Wendy, Vanhoutte, Leen, Neyt, Katrijn, Killeen, Nigel, Malissen, Bernard, Hammad, Hamida, Lambrecht, Bart N.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 21.02.2013; Elsevier Limited
• Subjects: Administration, Inhalation; Adoptive Transfer; Allergens - immunology; Allergens - isolation & purification; Allergies; Animals; Antigens, Dermatophagoides - administration & dosage; Antigens, Dermatophagoides - immunology; Antigens, Dermatophagoides - isolation & purification; Antigens, Ly - genetics; Antigens, Ly - immunology; Asthma - immunology; Asthma - pathology; Bone marrow; CD11b Antigen - genetics; CD11b Antigen - immunology; Cell growth; Cell Movement; Cell Proliferation; Chemokines; Dendritic Cells - immunology; Dendritic Cells - transplantation; Dermatophagoides pteronyssinus; Gene Expression; Immune system; Immunity, Cellular; Inflammation - immunology; Inflammation - pathology; Lung - immunology; Lung - pathology; Lymph Nodes - immunology; Lymph Nodes - pathology; Mice; Mice, Transgenic; Monocytes - immunology; Monocytes - transplantation; Natural Cytotoxicity Triggering Receptor 1 - genetics; Natural Cytotoxicity Triggering Receptor 1 - immunology; Organ Specificity; Pyroglyphidae - immunology; Receptors, IgG - genetics; Receptors, IgG - immunology; Th2 Cells - immunology; Transgenic animals
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2012.10.016

Dendritic cells (DCs) are crucial for mounting allergic airway inflammation, but it is unclear which subset of DCs performs this task. By using CD64 and MAR-1 staining, we reliably separated CD11b+ monocyte-derived DCs (moDCs) from conventional DCs (cDCs) and studied antigen uptake, migration, and presentation assays of lung and lymph node (LN) DCs in response to inhaled house dust mite (HDM). Mainly CD11b+ cDCs but not CD103+ cDCs induced T helper 2 (Th2) cell immunity in HDM-specific T cells in vitro and asthma in vivo. Studies in Flt3l−/− mice, lacking all cDCs, revealed that moDCs were also sufficient to induce Th2 cell-mediated immunity but only when high-dose HDM was given. The main function of moDCs was the production of proinflammatory chemokines and allergen presentation in the lung during challenge. Thus, we have identified migratory CD11b+ cDCs as the principal subset inducing Th2 cell-mediated immunity in the LN, whereas moDCs orchestrate allergic inflammation in the lung. ▸ CD64 and MAR-1 are optimum markers for separating moDCs from cDCs ▸ CD11b+ cDCs, not CD103+ cDCs, induce Th2 cell priming in lung ▸ moDCs, not cDCs, are the source of proinflammatory chemokines ▸ moDCs are not the exclusive APC for Th1 cell induction