Dendritic cell migration
Initiation of adaptive immune responses is dependent upon the activation of antigen-specific T cells by antigen-presenting cells including B cells, macrophages and dendritic cells. Dendritic cells are strategically present as sentinels in peripheral tissues at sites of pathogen entry, and have a unique migratory capacity allowing them to readily mobilize to lymph nodes where they encounter naIve or central memory T cells. Antigen-bearing dendritic cells typically gain access to lymph nodes via emigration through the afferent lymphatic vessels. Our laboratory is addressing the mechanisms that control the migration of dendritic cells to lymph nodes, a fundamental issue in immunology that will benefit clinical research aiming to manipulate immune responses and manage chronic inflammatory diseases.

We discovered that some lipid mediators can govern the migration of dendritic cells. More recently, we have studied the mobilization of dendritic cells in atherosclerosis, a chronic inflammation of the arterial wall characterized by an alteration in lipid mediators. Our findings suggest that dyslipidemia related to atherosclerosis severely impairs the emigration of dendritic cells to the lymph nodes. The retention of dendritic cells at the peripheral site may contribute to the local inflammation. Currently, the cellular and molecular events that trigger the impairment of dendritic cell migration are under investigation.

Although it is clear that lymphatic vessels are required for peripheral dendritic cells to enter lymph nodes, remarkably little research has been devoted to investigate whether lymphatic vessel function may regulate the process of dendritic cell migration in normal and inflammatory conditions. We have recently shown that inflammatory signals present in a strong adjuvant induce lymph node swelling accompanied by Iymphangiogenesis. This expansion of lymphatics leads to a more robust migration of dendritic cells and is, surprisingly, dependent on the recruitment of B cells within the activated lymph node. Understanding how lymphatic vessel function may affect adaptive immune response by modulating dendritic cell migration is another focus of our work.

Quemeneur L, Angeli V, Chopin M and Jessberger R (2008) SWAP-70 deficiency causes high-affinity plasma cell generation despite impaired germinal center formation. Blood. 111:2714-24

Angeli V, Ginhoux F, LlOdraJ, Quemeneur L, Frenette PS, Skobe M, Jessberger R, Merad M and GJ Randolph (2006) B cell driven lymphangiogenesis in inflamed lymph nodes enhances dendritic cell mobilization. Immunity. 24: 203-215

Randolph GJ, Angeli V and Swartz MA (2005) Dendritic cell trafficking to lymph nodes through lymphatic vessels. Nat. Rev. Immunol. 5:617-628

Randolph GJ, Sanchez-Schmitz G and Angeli V (2005) Factors and signals that govern the migration of dendritic cells via lymphatics: recent advances. Springer Semin. Immunopathol. 26:273-287

Angeli V, Llodra J, Rong JX, Satoh K, Ishii S, Shimizu T, Fisher EA and Randolph GJ (2004) Dyslipidemia associated with atherosclerotic disease systemically alters dendritic cell mobilization. Immunity. 21:561-574

Llodra J, Angeli V, Liu J, Trogan E, Fisher EA and Randolph GJ (2004) Emigration of monocyte-derived cells from atherosclerotic lesions of mice characterizes regressive, but not progressive, plaques. Proc. Nat. Acad. Sci. 101:11779-11784

Trottein F, Faveeuw C, Gosset P and Angeli V (2004) Role of the prostanoid receptor 1 in the modulation of immune and inflammatory responses. Crit. Rev. Immunol. 24:349-362

Angeli V, Staumont D, Charbonnier AS, Hammad H, Gosset P, Pichavant M, Lambrecht BN, Capron M, Dombrowicz D and Trottein F (2004) Activation of the D prostanoid receptor 1 regulates immune and skin allergic responses. J. Immunol. 172:3822-3829

Angeli V, Faveeuw C, Roye 0, Fontaine J, Capron A, Wolowczuk I, Capron M and Trottein F (2001) Role of the parasite derived-PGDz in the inhibition of epidermal Langerhans cell migration during schistosomiasis infection. J. Exp. Med. 193:1135-1148