RANTES-induced chemokine cascade in dendritic cells

F. R. Fischer, Y. Luo, M. Luo, Laura Santambrogio, M. E. Dorf

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Dendritic cells (DC) are the most potent APCs and the principal activators of naive T cells. We now report that chemokines can serve as activating agents for immature DC. Murine bone marrow-derived DC respond to the CC chemokine RANTES (10-100 ng/ml) by production of proinflammatory mediators. RANTES induces rapid expression of transcripts for the CXC chemokines KC and macrophage inflammatory protein (MIP)-2, the CC chemokines MIP-1β and MIP-1α, and the cytokines TNF-α and IL-6. Synthesis of KC, IL-6, and TNF-α proteins were also demonstrated. After 4 h, autoinduction of RANTES transcripts was observed. These responses are chemokine specific. Although DC demonstrated weak responses to eotaxin, DC failed to respond to other chemokines including KC, MIP-2, stromal-derived factor-1α, MIP-1β, MIP-1α, monocyte chemoattractant protein-1, T cell activation gene 3, or thymus-derived chemotactic agent 4. In addition, RANTES treatment up-regulated expression of an orphan chemokine receptor termed Eo1. Chemokine induction was also observed after treatment of splenic DC and neonatal microglia with RANTES, but not after treatment of thymocytes or splenocytes depleted of adherent cells. TNF-α-treated DC lose responsiveness to RANTES. DC from mice deficient for CCR1, CCR3, and CCR5 respond to RANTES, indicating that none of these receptors are exclusively used to initiate the chemokine cascade. RANTES-mediated chemokine amplification in DC may prolong inflammatory responses and shape the microenvironment, potentially enhancing acquired and innate immune responses.

Original languageEnglish (US)
Pages (from-to)1637-1643
Number of pages7
JournalJournal of Immunology
Volume167
Issue number3
StatePublished - Aug 1 2001
Externally publishedYes

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Chemokine CCL5
Chemokines
Dendritic Cells
Macrophage Inflammatory Proteins
Chemokine CXCL2
CC Chemokines
Interleukin-6
Chemokine CCL21
T-Lymphocytes
CXC Chemokines
Chemokine CCL2
Chemokine Receptors
Microglia
Thymocytes
Innate Immunity
Transcriptional Activation
Bone Marrow
Cytokines

ASJC Scopus subject areas

  • Immunology

Cite this

Fischer, F. R., Luo, Y., Luo, M., Santambrogio, L., & Dorf, M. E. (2001). RANTES-induced chemokine cascade in dendritic cells. Journal of Immunology, 167(3), 1637-1643.

RANTES-induced chemokine cascade in dendritic cells. / Fischer, F. R.; Luo, Y.; Luo, M.; Santambrogio, Laura; Dorf, M. E.

In: Journal of Immunology, Vol. 167, No. 3, 01.08.2001, p. 1637-1643.

Research output: Contribution to journalArticle

Fischer, FR, Luo, Y, Luo, M, Santambrogio, L & Dorf, ME 2001, 'RANTES-induced chemokine cascade in dendritic cells', Journal of Immunology, vol. 167, no. 3, pp. 1637-1643.
Fischer FR, Luo Y, Luo M, Santambrogio L, Dorf ME. RANTES-induced chemokine cascade in dendritic cells. Journal of Immunology. 2001 Aug 1;167(3):1637-1643.
Fischer, F. R. ; Luo, Y. ; Luo, M. ; Santambrogio, Laura ; Dorf, M. E. / RANTES-induced chemokine cascade in dendritic cells. In: Journal of Immunology. 2001 ; Vol. 167, No. 3. pp. 1637-1643.
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