PMID- 31287961 OWN - NLM STAT- MEDLINE DCOM- 20200601 LR - 20200601 IS - 1530-6860 (Electronic) IS - 0892-6638 (Linking) VI - 33 IP - 10 DP - 2019 Oct TI - Pdlim4 is essential for CCR7-JNK-mediated dendritic cell migration and F-actin-related dendrite formation. PG - 11035-11044 LID - 10.1096/fj.201901031 [doi] AB - 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. FAU - Yoo, Ji-Young AU - Yoo JY AD - Department of Biotechnology, CHA University, Seongnam, South Korea. FAU - Jung, Nam-Chul AU - Jung NC AD - Department of Biotechnology, CHA University, Seongnam, South Korea. AD - Pharos Vaccine, Seongnam, South Korea. FAU - Lee, Jun-Ho AU - Lee JH AD - Pharos Vaccine, Seongnam, South Korea. FAU - Choi, So-Yeon AU - Choi SY AD - Department of Biotechnology, CHA University, Seongnam, South Korea. FAU - Choi, Hyun-Ji AU - Choi HJ AD - JW CreaGene Company, Seongnam, South Korea. FAU - Park, Soo-Yeoun AU - Park SY AD - Aprogen, Seongnam, South Korea. FAU - Jang, Ji-Su AU - Jang JS AD - Department of Biotechnology, CHA University, Seongnam, South Korea. FAU - Byun, Sei-Hee AU - Byun SH AD - Aprogen, Seongnam, South Korea. FAU - Hwang, Sung-Uk AU - Hwang SU AD - Pharos Vaccine, Seongnam, South Korea. FAU - Noh, Kyung-Eun AU - Noh KE AD - Department of Biotechnology, CHA University, Seongnam, South Korea. FAU - Park, Yunok AU - Park Y AD - Department of Biotechnology, CHA University, Seongnam, South Korea. FAU - Lee, Jongwon AU - Lee J AD - Department of Biotechnology, CHA University, Seongnam, South Korea. FAU - Song, Jie-Young AU - Song JY AD - Department of Radiation Cancer Sciences, Korea Institute of Radiological and Medical Sciences, Seoul, South Korea. FAU - Seo, Han Geuk AU - Seo HG AD - Department of Food Science and Biotechnology of Animal Resources, Sanghuh College of Life Sciences, Konkuk University, Seoul, South Korea. FAU - Lee, Hyun Soo AU - Lee HS AD - Pharos Vaccine, Seongnam, South Korea. FAU - Lim, Dae-Seog AU - Lim DS AD - Department of Biotechnology, CHA University, Seongnam, South Korea. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190709 PL - United States TA - FASEB J JT - FASEB journal : official publication of the Federation of American Societies for Experimental Biology JID - 8804484 RN - 0 (Actins) RN - 0 (Ccr7 protein, mouse) RN - 0 (LIM Domain Proteins) RN - 0 (Microfilament Proteins) RN - 0 (Pdlim4 protein, mouse) RN - 0 (Receptors, CCR7) RN - EC 2.7.12.2 (MAP Kinase Kinase 4) SB - IM MH - Actins/metabolism MH - Animals MH - *Cell Movement MH - Cells, Cultured MH - Dendritic Cells/immunology/*metabolism/physiology MH - LIM Domain Proteins/genetics/*metabolism MH - Lymphocyte Activation MH - MAP Kinase Kinase 4/metabolism MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Microfilament Proteins/genetics/*metabolism MH - Receptors, CCR7/metabolism OTO - NOTNLM OT - DC marker OT - DC maturation OT - DCs EDAT- 2019/07/10 06:00 MHDA- 2020/06/02 06:00 CRDT- 2019/07/10 06:00 PHST- 2019/07/10 06:00 [pubmed] PHST- 2020/06/02 06:00 [medline] PHST- 2019/07/10 06:00 [entrez] AID - 10.1096/fj.201901031 [doi] PST - ppublish SO - FASEB J. 2019 Oct;33(10):11035-11044. doi: 10.1096/fj.201901031. Epub 2019 Jul 9.