Microbial Stimulation Fully Differentiates Monocytes to DC-SIGN/CD209⁺ Dendritic Cells for Immune T Cell Areas

Cheolho Cheong, et al, Cell. 2010. 143:416-429

Speaker：Yu-Chang Chang (張育菖)                                       Time：14:10~15:00, Jun. 1, 2011

Commentator：Chun-Keung Yu, Ph.D. (余俊強 博士)  Place：Room 601

Abstract:

Dendritic cells (DCs) are immune cells that are specialized to capture and present antigens to T lymphocytes in order to mediate immunity or tolerance¹. In the bone marrow, a common myeloid progenitor gives rise to monocytes and other precursors termed pre-cDCs². Pre-cDCs move into the blood to form CD11c^hi, MHC II^hi DCs. Monocytes, although first studied as macrophage precursors, also can differentiate into DCs termed monocyte-derived DCs (Mo-DCs) upon culture in interleukin-4 (IL-4) and granulocyte macrophage colony-stimulating factor (GM-CSF)³. Nevertheless, the role of Mo-DCs in induction of T cell responses in vivo remains unclear. In this study, the authors showed that monocytes could fully differentiate into Mo-DCs in combined stimulation of IL-4 and GM-CSF, by which Mo-DCs showed rapidly lost expression of monocyte markers and acquired the probing morphology of DCs. Besides, DC-SIGN/CD209a marked Mo-DCs with strong antigen-presenting activity to T cells, including cross-presentation. In response to injection of lipopolysaccharide (LPS) or gram-negative bacteria in vivo, Mo-DCs were recruited from blood monocytesinto the T cell areas of lymph nodes. The authors further characterized the mechanism of Mo-DCs mobilization, and found that L-selectin and CCR7 were required for LPS to generate Mo-DCs. Meanwhile, TLR4 and its co-receptor CD14, a needed co-receptor for Trif-dependent LPS signaling, were markedly up-regulated in Mo-DCs. Moreover, CD14^-/- mice failed to mobilize Mo-DCs in response to LPS. Taken together, they demonstrate that LPS-induced differentiation of CD209-marked Mo-DCs requires L-selectin and CCR7, and up-regulated CD14 is essential for Mo-DCs differentiation via Trif signaling.

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2.      Liu K, et al, Science. 2009. 324:392-397.

3.      Sallusto F, Lanzavecchia A. J Exp Med. 1994. 179:1109-1118.