PMID- 18025190 OWN - NLM STAT- MEDLINE DCOM- 20080205 LR - 20190516 IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 179 IP - 11 DP - 2007 Dec 1 TI - Functional role of P-selectin glycoprotein ligand 1/P-selectin interaction in the generation of tolerogenic dendritic cells. PG - 7457-65 AB - Dendritic cells (DCs) have a key role in both the generation of the immune response and the induction of tolerance to self-Ags. In this work, the possible role of P-selectin glycoprotein ligand 1 (PSGL-1) on the tolerogenic activity of human DCs was explored. We found that the engagement of PSGL-1 by P-selectin on DCs induced the expression of c-Fos, IDO, IL-10, and TGF-beta genes. Remarkably, stimulation of DCs through PSGL-1 with P-selectin enhanced their capability to generate CD4(+)CD25(+)Foxp3(+) regulatory T cells, which expressed high levels of TGF-beta1 mRNA, synthesized IL-10, and suppressed the proliferation of autologous CD4(+)CD25(-) T cells. Accordingly, we found that DCs from PSGL-1(-/-) mice expressed higher levels of MHC class II molecules, and exhibited an enhanced immunogenicity compared with wild-type mice. In addition, the percentage of CD4(+)CD25(+)Foxp3(+) regulatory T cells in the thymus of PSGL-1-deficient animals was significantly reduced. Our data reveal an unexpected role of PSGL-1 on the tolerogenic function of DCs, and the regulation of the immune response. FAU - Urzainqui, Ana AU - Urzainqui A AD - Servicio de Inmunologia, Hospital Universitario de La Princesa, Universidad Autonoma de Madrid, Madrid, Spain. FAU - Martinez del Hoyo, Gloria AU - Martinez del Hoyo G FAU - Lamana, Amalia AU - Lamana A FAU - de la Fuente, Hortensia AU - de la Fuente H FAU - Barreiro, Olga AU - Barreiro O FAU - Olazabal, Isabel M AU - Olazabal IM FAU - Martin, Pilar AU - Martin P FAU - Wild, Martin K AU - Wild MK FAU - Vestweber, Dietmar AU - Vestweber D FAU - Gonzalez-Amaro, Roberto AU - Gonzalez-Amaro R FAU - Sanchez-Madrid, Francisco AU - Sanchez-Madrid F LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Forkhead Transcription Factors) RN - 0 (Foxp3 protein, mouse) RN - 0 (Indoleamine-Pyrrole 2,3,-Dioxygenase) RN - 0 (Membrane Glycoproteins) RN - 0 (P-Selectin) RN - 0 (P-selectin ligand protein) RN - 0 (Proto-Oncogene Proteins c-fos) RN - 0 (RNA, Messenger) RN - 0 (Transforming Growth Factor beta) RN - 0 (Transforming Growth Factor beta1) RN - 130068-27-8 (Interleukin-10) SB - IM MH - Animals MH - Cells, Cultured MH - Dendritic Cells/drug effects/immunology MH - Female MH - Forkhead Transcription Factors/immunology MH - Gene Expression Regulation/genetics MH - Immune Tolerance/*immunology MH - Indoleamine-Pyrrole 2,3,-Dioxygenase/genetics MH - Interleukin-10/genetics MH - Male MH - Membrane Glycoproteins/biosynthesis/genetics/*physiology MH - Mice MH - Mice, Inbred C57BL MH - P-Selectin/*metabolism/pharmacology MH - Protein Binding MH - Proto-Oncogene Proteins c-fos/genetics MH - RNA, Messenger/genetics MH - T-Lymphocytes, Regulatory/immunology MH - Transforming Growth Factor beta/genetics MH - Transforming Growth Factor beta1/genetics EDAT- 2007/11/21 09:00 MHDA- 2008/02/06 09:00 CRDT- 2007/11/21 09:00 PHST- 2007/11/21 09:00 [pubmed] PHST- 2008/02/06 09:00 [medline] PHST- 2007/11/21 09:00 [entrez] AID - 179/11/7457 [pii] AID - 10.4049/jimmunol.179.11.7457 [doi] PST - ppublish SO - J Immunol. 2007 Dec 1;179(11):7457-65. doi: 10.4049/jimmunol.179.11.7457.