title: Transcriptional and functional characterization of CD137L-dendritic cells identifies a novel dendritic cell phenotype.
abstract: The importance of monocyte-derived dendritic cells (DCs) is evidenced by the fact that they are essential for the elimination of pathogens. Although in vitro DCs can be generated by treatment of monocytes with GM-CSF and IL-4, it is unknown what stimuli induce differentiation of DCs in vivo. CD137L-DCs are human monocyte-derived DC that are generated by CD137 ligand (CD137L) signaling. We demonstrate that the gene signature of in vitro generated CD137L-DCs is most similar to those of GM-CSF and IL-4-generated immature DCs and of macrophages. This is reminiscent of in vivo inflammatory DC which also have been reported to share gene signatures with monocyte-derived DCs and macrophages. Performing direct comparison of deposited human gene expression data with a CD137L-DC dataset revealed a significant enrichment of CD137L-DC signature genes in inflammatory in vivo DCs. In addition, surface marker expression and cytokine secretion by CD137L-DCs resemble closely those of inflammatory DCs. Further, CD137L-DCs express high levels of adhesion molecules, display strong attachment, and employ the adhesion molecule ALCAM to stimulate T cell proliferation. This study characterizes the gene expression profile of CD137L-DCs, and identifies significant similarities of CD137L-DCs with in vivo inflammatory monocyte-derived DCs and macrophages.
authors.affiliation: Department of Physiology, National University of Singapore, Singapore.|NUS Immunology Programme, Life Sciences Institute, National University of Singapore, Singapore.|NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore.
authors.forename: Zulkarnain
authors.initials: Z
authors.lastname: Harfuddin
authors.affiliation: Department of Physiology, National University of Singapore, Singapore.|NUS Immunology Programme, Life Sciences Institute, National University of Singapore, Singapore.
authors.forename: Bhushan
authors.initials: B
authors.lastname: Dharmadhikari
authors.affiliation: NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore.
authors.forename: Siew Cheng
authors.initials: SC
authors.lastname: Wong
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research, Singapore.
authors.forename: Kaibo
authors.initials: K
authors.lastname: Duan
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research, Singapore.
authors.forename: Michael
authors.initials: M
authors.lastname: Poidinger
authors.affiliation: Department of Physiology, National University of Singapore, Singapore.|NUS Immunology Programme, Life Sciences Institute, National University of Singapore, Singapore.
authors.forename: Shaqireen
authors.initials: S
authors.lastname: Kwajah
authors.affiliation: Department of Physiology, National University of Singapore, Singapore.|NUS Immunology Programme, Life Sciences Institute, National University of Singapore, Singapore.|NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore.
authors.forename: Herbert
authors.initials: H
authors.lastname: Schwarz
mesh_terms: D053330:4-1BB Ligand / Q000235:genetics* / Q000378:metabolism; D020410:Activated-Leukocyte Cell Adhesion Molecule / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000378:metabolism*; D020869:Gene Expression Profiling / Q000379:methods; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology; D009000:Monocytes / Q000378:metabolism*; D010641:Phenotype; D015398:Signal Transduction / Q000235:genetics; D015533:Transcriptional Activation
chemical_list: D053330:4-1BB Ligand; D020410:Activated-Leukocyte Cell Adhesion Molecule; D016207:Cytokines; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor