PMID- 20404167 OWN - NLM STAT- MEDLINE DCOM- 20100608 LR - 20211020 IS - 1091-6490 (Electronic) IS - 0027-8424 (Print) IS - 0027-8424 (Linking) VI - 107 IP - 18 DP - 2010 May 4 TI - Selective and site-specific mobilization of dermal dendritic cells and Langerhans cells by Th1- and Th2-polarizing adjuvants. PG - 8334-9 LID - 10.1073/pnas.0912817107 [doi] AB - Dendritic cells (DCs) initiate and polarize adaptive immune responses toward varying functional outcomes. By means of intravital two-photon microscopy, we report that dermal dendritic cells (DDCs) and Langerhans cells (LCs) are differentially mobilized during contact sensitization and by adjuvants such as unmethylated CpG oligonucleotide (CpG) and LPS that induce T helper type 1 (Th1) responses, or papain that induces T helper type 2 (Th2) responses. In ear pinna, contact sensitization, CpG, LPS, and papain all mobilized DDCs in three distinct phases: increased motility and dendritic probing, directed migration, and entry into lymphatic vessels. During the same treatments, the adjacent LCs in ear pinna remained immotile over a 48-hr period of observation. In contrast, footpads lacked DDCs and Th1-polarizing adjuvants selectively induced a delayed mobilization of LCs after 48 hr. Th1 polarization of CD4(+) T cells was independent of the immunization site, whereas ear immunization favored Th2 polarization, correlating with site-specific DC distribution and dynamics. Our results provide an initial description of peripheral DC dynamics in response to adjuvants and imply that LC mobilization enhances a Th1 response and is not sufficient to trigger a Th2 response, whereas mobilization of DDCs alone is sufficient to trigger T-cell proliferation and to polarize initial T-cell activation toward a Th2 response. FAU - Sen, Debasish AU - Sen D AD - Department of Physiology and Biophysics and Institute for Immunology, University of California, Irvine, CA 92697-4561, USA. FAU - Forrest, Luette AU - Forrest L FAU - Kepler, Thomas B AU - Kepler TB FAU - Parker, Ian AU - Parker I FAU - Cahalan, Michael D AU - Cahalan MD LA - eng GR - GM-41514/GM/NIGMS NIH HHS/United States GR - R01 GM048071/GM/NIGMS NIH HHS/United States GR - R37 GM048071/GM/NIGMS NIH HHS/United States GR - R01 GM041514/GM/NIGMS NIH HHS/United States GR - N01AI50019/AI/NIAID NIH HHS/United States GR - GM-48071/GM/NIGMS NIH HHS/United States GR - P30 CA062203/CA/NCI NIH HHS/United States GR - N01-AI-50019/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20100419 PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (CPG-oligonucleotide) RN - 0 (Lipopolysaccharides) RN - 0 (Oligodeoxyribonucleotides) SB - IM MH - Animals MH - Cell Movement MH - *Cell Polarity MH - Cell Proliferation MH - Coculture Techniques MH - Langerhans Cells/cytology/*immunology MH - Lipopolysaccharides/immunology MH - Lymphocyte Activation MH - Mice MH - Mice, Inbred C57BL MH - Oligodeoxyribonucleotides/immunology MH - Th1 Cells/*cytology/*immunology MH - Th2 Cells/*cytology/*immunology PMC - PMC2889549 COIS- The authors declare no conflict of interest. EDAT- 2010/04/21 06:00 MHDA- 2010/06/09 06:00 PMCR- 2010/11/04 CRDT- 2010/04/21 06:00 PHST- 2010/04/21 06:00 [entrez] PHST- 2010/04/21 06:00 [pubmed] PHST- 2010/06/09 06:00 [medline] PHST- 2010/11/04 00:00 [pmc-release] AID - 0912817107 [pii] AID - 200912817 [pii] AID - 10.1073/pnas.0912817107 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 2010 May 4;107(18):8334-9. doi: 10.1073/pnas.0912817107. Epub 2010 Apr 19.