Dendritic cells play a key role in the adaptive immune system by influencing T-cell differentiation. Annexin-1 (Anx-A1) has recently been shown to modulate the adaptive immune response by regulating T-cell activation and differentiation. Here we investigated the role of endogenous Anx-A1 in dendritic cells as major cellular counterpart of T-cell-driven immune response. We found that Anx-A1 −/− bone marrow-derived dendritic cells show an increased number of CD11c + cells expressing high levels of some maturation markers, such as CD40, CD54, and CD80, coupled to a decreased capacity to take up antigen compared to control Anx-A1 +/+ cells. However, analysis of LPS-treated dendritic cells from Anx-A1 −/− mice demonstrated a diminished up-regulation of maturation markers, a decreased migratory activity in vivo , and an attenuated production of the inflammatory cytokines interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and IL-12. This defect was also accompanied by impaired nuclear factor (NF)-κB/DNA-binding activity and lack of Anx-A1 signaling, as demonstrated by the reduced activation of extracellular-signal regulated kinase (ERK)1/2 and Akt compared to cells from control littermates. As a consequence of this phenotype, Anx-A1 −/− dendritic cells showed an impaired capacity to stimulate T-cell proliferation and differentiation in mixed leukocyte reaction. Together, these findings suggest that inhibition of Anx-A1 expression or function in dendritic cells might represent a useful way to modulate the adaptive immune response and pathogen-induced T-cell-driven immune diseases.—Huggins, A., Paschalidis, N., Flower, R. J., Perretti, M., D'Acquisto, F. Annexin-1-deficient dendritic cells acquire a mature phenotype during differentiation.
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Annexin-1-deficient dendritic cells acquire a mature phenotype during differentiation
Huggins, Anthony; Paschalidis, Nikolaos; Flower, Roderick J.; Perretti, Mauro; D'Acquisto, Fulvio
Follow The FASEB Journal
, Volume 23 (4): 985
Fed of American Socs for Experimental Biology – Apr 1, 2009
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