A single subset of dendritic cells controls the cytokine bias of natural killer T cell responses to diverse glycolipid antigens

Pooja Arora, Andres Baena, Karl O.A. Yu, Neeraj K. Saini, Shalu S. Kharkwal, Michael F. Goldberg, Shajo Kunnath-Velayudhan, Leandro J. Carreño, Manjunatha M. Venkataswamy, John Kim, Eszter Lazar-Molnar, Gregoire Lauvau, Young tae Chang, Zheng Liu, Robert Bittman, Aymen Al-Shamkhani, Liam R. Cox, Peter J. Jervis, Natacha Veerapen, Gurdyal S. BesraSteven A. Porcelli

Research output: Contribution to journalArticlepeer-review

88 Scopus citations

Abstract

Many hematopoietic cell types express CD1d and are capable of presenting glycolipid antigens to invariant natural killer Tcells (iNKT cells). However, the question of which cells are the principal presenters of glycolipid antigens invivo 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.

Original languageEnglish (US)
Pages (from-to)105-116
Number of pages12
JournalImmunity
Volume40
Issue number1
DOIs
StatePublished - Jan 16 2014

Bibliographical note

Funding Information:
This work was supported by NIH/NIAID grant AI45889 to S.A.P. Flow cytometry and imaging studies were carried out with analytical imaging and FACS core facilities supported by the Einstein Cancer Center (NIH/NCI CA013330) and the Einstein Center for AIDS Research (NIH AI-51519). S. pneumoniae URF918 was provided by M. Kronenberg (La Jolla Institute for Allergy & Immunology). G.S.B was supported by a Personal Research Chair from James Bardrick, a Royal Society Wolfson Research Merit Award, the Wellcome Trust (084923/B/08/7), and the MRC (G1001750). A.B. acknowledges support from Programa Estrategia de Sostenibilidad, Universidad de Antioquia, Medellín, Colombia. S.A.P. has served as paid consultants for Vaccinex, which has an interest in the commercial development of iNKT cell targeted therapeutics. We thank Olisambu Uche for help with FACS sorting.

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