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Peripheral CD103+ dendritic cells form a unified subset developmentally related to CD8alpha+ conventional dendritic cells.

ABSTRACT: Although CD103-expressing dendritic cells (DCs) are widely present in nonlymphoid tissues, the transcription factors controlling their development and their relationship to other DC subsets remain unclear. Mice lacking the transcription factor Batf3 have a defect in the development of CD8alpha+ conventional DCs (cDCs) within lymphoid tissues. We demonstrate that Batf3(-/-) mice also lack CD103+CD11b- DCs in the lung, intestine, mesenteric lymph nodes (MLNs), dermis, and skin-draining lymph nodes. Notably, Batf3(-/-) mice displayed reduced priming of CD8 T cells after pulmonary Sendai virus infection, with increased pulmonary inflammation. In the MLNs and intestine, Batf3 deficiency resulted in the specific lack of CD103+CD11b- DCs, with the population of CD103+CD11b+ DCs remaining intact. Batf3(-/-) mice showed no evidence of spontaneous gastrointestinal inflammation and had a normal contact hypersensitivity (CHS) response, despite previous suggestions that CD103+ DCs were required for immune homeostasis in the gut and CHS. The relationship between CD8alpha+ cDCs and nonlymphoid CD103+ DCs implied by their shared dependence on Batf3 was further supported by similar patterns of gene expression and their shared developmental dependence on the transcription factor Irf8. These data provide evidence for a developmental relationship between lymphoid organ-resident CD8alpha+ cDCs and nonlymphoid CD103+ DCs.

SUBMITTER: Edelson BT

PROVIDER: S-EPMC2856032 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature

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Peripheral CD103+ dendritic cells form a unified subset developmentally related to CD8alpha+ conventional dendritic cells.

Edelson Brian T BT KC Wumesh W Juang Richard R Kohyama Masako M Benoit Loralyn A LA Klekotka Paul A PA Moon Clara C Albring Jörn C JC Ise Wataru W Michael Drew G DG Bhattacharya Deepta D Stappenbeck Thaddeus S TS Holtzman Michael J MJ Sung Sun-Sang J SS Murphy Theresa L TL Hildner Kai K Murphy Kenneth M KM

The Journal of experimental medicine 20100329 4

Although CD103-expressing dendritic cells (DCs) are widely present in nonlymphoid tissues, the transcription factors controlling their development and their relationship to other DC subsets remain unclear. Mice lacking the transcription factor Batf3 have a defect in the development of CD8alpha+ conventional DCs (cDCs) within lymphoid tissues. We demonstrate that Batf3(-/-) mice also lack CD103+CD11b- DCs in the lung, intestine, mesenteric lymph nodes (MLNs), dermis, and skin-draining lymph nodes ...[more]

PMID: 20351058

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Project description:Advanced non-small cell lung cancer (NSCLC) leads to a high death rate in patients and is a major threat to human health. NSCLC induces an immune suppressive microenvironment and escapes from immune surveillance in vivo. At present, the molecular mechanisms of NSCLC immunopathogenesis and the immune suppressive microenvironment induced by NSCLC have not been fully elucidated. Here, we focus on the effect of NSCLC cells on the development and differentiation of human CD1c+ conventional dendritic cell (DC) subsets mediated by CD205 and CD103. The peripheral blood mononuclear cells (PBMCs) were isolated from NSCLC patients and healthy donors. DCs were induced and cocultured with primary NSCLC cells or tumor cell line H1299. DCs without incubation with tumor cells are control. The protein expression of costimulatory molecules such as CD80 and CD86, HLA-DR, pro-/anti-inflammatory cytokines such as IL-10 and IL-12, and CD205 and CD103 on CD1c+ DCs was detected by flow cytometry. Our data revealed two new subpopulations of human CD1c+ DCs (CD1c+CD205+CD103+ and CD1c+CD205+CD103- DC) in healthy donors and NSCLC patients. NSCLC cells modulate the development of the CD1c+CD205+CD103+ DC and CD1c+CD205+CD103- DC subpopulations in vitro and ex vivo. NSCLC cells also suppress the expression of signal molecules such as CD40, CD80, CD86, and HLA-DR on CD1c+ DCs. In addition, the production of pro-inflammatory cytokines, including IL-12 and IL-23, is downregulated by NSCLC cells; however, the secretion of anti-inflammatory cytokines, such as IL-10 and IL-27, by CD1c+ DCs is upregulated by NSCLC cells. Our results suggest that NSCLC cells may induce immune tolerogenic DCs, which block DC-mediated anti-tumor immunity in NSCLC patients. Our data may be helpful in revealing new cellular mechanisms related to the induction of tolerogenic CD1c+ DCs by NSCLCs and the development of an immune suppressive microenvironment that causes tumor cells to escape immune surveillance. Our results indicate a potential role for CD1c+ DC subsets mediated by CD205 and CD103 in DC-mediated immunotherapy to target NSCLC in the future.

Dataset Information

Peripheral CD103+ dendritic cells form a unified subset developmentally related to CD8alpha+ conventional dendritic cells.

Publications

Peripheral CD103+ dendritic cells form a unified subset developmentally related to CD8alpha+ conventional dendritic cells.

Similar Datasets

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