Pdlim4 is essential for CCR7-JNK-mediated dendritic cell migration and F-actin-related dendrite formation.

Dendritic cells (DCs) are the most potent professional antigen (Ag)-presenting cells and inducers of T cell-mediated immunity. A previous microarray analysis identified PDZ and LIM domain protein 4 (Pdlim4) as a candidate marker for DC maturation. The aim of this study was to investigate whether Pdlim4 influences DC migration and maturation. Mouse bone marrow-derived DCs were transduced lentivirally with Pdlim4 short hairpin RNA and examined by confocal microscopy, flow cytometry, ELISA, and Western blotting. Pdlim4 was highly induced in LPS-stimulated mature DCs (mDCs). Pdlim4-knockdown mDCs showed reduced expression of molecules associated with Ag presentation and T-cell costimulation, reduced cytokine production, and functional defects in their ability to activate T cells. Moreover, Pdlim4 was necessary for mDC migration via C-C chemokine receptor type 7 (CCR7)-JNK in in vitro Transwell assays. The importance of Pdlim4 in DC migration was confirmed with an in vivo migration model in which C57BL/6 mice were injected with fluorescently labeled DCs in the footpad and migration to the popliteal lymph nodes was assessed by flow cytometry. Moreover, dendrite formation in mDCs was remarkably attenuated under Pdlim4 knockdown. Taken together, these results demonstrate that Pdlim4 is necessary for DC migration via CCR7-JNK, dendrite formation, and subsequent development of functional T-cell responses.-Yoo, J.-Y., Jung, N.-C., Lee, J.-H., Choi, S.-Y., Choi, H.-J., Park, S.-Y., Jang, J.-S., Byun, S.-H., Hwang, S.-U., Noh, K.-E., Park, Y., Lee, J., Song, J.-Y., Seo, H. G., Lee, H. S., Lim, D.-S. Pdlim4 is essential for CCR7-JNK-mediated dendritic cell migration and F-actin-related dendrite formation.

Rosiglitazone-mediated dendritic cells ameliorate collagen-induced arthritis in mice.

Rosiglitazone is a selective ligand for peroxisome proliferator-activated receptor-gamma (PPAR-γ), which serves diverse biological functions. A number of autoimmune disease models have been used to examine the anti-inflammatory and immunosuppressive effects of tolerogenic dendritic cells (tDCs). The aim of the present study was to investigate whether rosiglitazone-mediated DC (Rosi-DC) therapy suppressed arthritis in a collagen-induced arthritis (CIA) mouse model. Rosi-DCs were generated by treating immature DCs with TNF-α, type II collagen, and rosiglitazone. CIA mice then received subcutaneously (s.c.) two injections of Rosi-DCs. The severity of arthritis was then assessed histopathologically. The phenotypes of the DC and regulatory T (Treg) cell populations in CIA mice were determined by flow cytometry and the effect of Rosi-DCs on the secretion of autoimmunity-inducing cytokines was examined by ELISA. Rosi-DCs expressed lower levels of DC-related surface markers than mature DCs. Histopathological examination revealed that the degree of inflammation in the paws of Rosi-DC-treated mice was much lower than that in the paws of PBS-treated CIA mice. Taken together, these results clearly show that rosiglitazone-mediated DCs ameliorate CIA, most likely via the induction of antigen-specific Treg cells.