1. A Single Subset of Dendritic Cells Controls the Cytokine Bias of Natural Killer T Cell Responses to Diverse Glycolipid Antigens
- Author
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Manjunatha M. Venkataswamy, Natacha Veerapen, Liam R. Cox, Robert Bittman, Grégoire Lauvau, Andres Baena, Neeraj K. Saini, Eszter Lazar-Molnar, Shajo Kunnath-Velayudhan, Michael F. Goldberg, Shalu Sharma Kharkwal, Steven A. Porcelli, John Kim, Peter J. Jervis, Gurdyal S. Besra, Karl O.A. Yu, Leandro J. Carreño, Aymen Al-Shamkhani, Young-Tae Chang, Pooja Arora, and Zheng Liu
- Subjects
Cell signaling ,CD8 Antigens ,medicine.medical_treatment ,Immunology ,Antigen presentation ,Galactosylceramides ,Receptors, Cell Surface ,Cell Communication ,Lymphocyte Activation ,Article ,Minor Histocompatibility Antigens ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Glycolipid ,Antigen ,Antigens, CD ,medicine ,Homeostasis ,Animals ,Immunology and Allergy ,Lectins, C-Type ,Antigens ,030304 developmental biology ,Inflammation ,Mice, Knockout ,Antigen Presentation ,0303 health sciences ,biology ,Dendritic Cells ,Dendritic cell ,Natural killer T cell ,3. Good health ,Cell biology ,Mice, Inbred C57BL ,Infectious Diseases ,Cytokine ,Gene Expression Regulation ,CD1D ,biology.protein ,Cytokines ,Natural Killer T-Cells ,lipids (amino acids, peptides, and proteins) ,Antigens, CD1d ,030215 immunology - Abstract
Summary Many hematopoietic cell types express CD1d and are capable of presenting glycolipid antigens to invariant natural killer T cells (iNKT cells). However, the question of which cells are the principal presenters of glycolipid antigens in vivo remains controversial, and it has been suggested that this might vary depending on the structure of a particular glycolipid antigen. Here we have shown that a single type of cell, the CD8α+ DEC-205+ dendritic cell, was mainly responsible for capturing and presenting a variety of different glycolipid antigens, including multiple forms of α-galactosylceramide that stimulate widely divergent cytokine responses. After glycolipid presentation, these dendritic cells rapidly altered their expression of various costimulatory and coinhibitory molecules in a manner that was dependent on the structure of the antigen. These findings show flexibility in the outcome of two-way communication between CD8α+ dendritic cells and iNKT cells, providing a mechanism for biasing toward either proinflammatory or anti-inflammatory responses., Graphical Abstract, Highlights • Complexes of antigenic glycolipids bound to CD1d have been visualized in situ • A single DC subset predominates in presentation of a variety of glycolipids • Antigen presentation to iNKT cells rapidly alters accessory molecules on APCs • Reciprocal induction of CD70 and PD-L2 controls cytokine bias of iNKT cell responses
- Published
- 2014