PMID- 17371954 OWN - NLM STAT- MEDLINE DCOM- 20070619 LR - 20190516 IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 178 IP - 7 DP - 2007 Apr 1 TI - Cutting Edge: Immature human dendritic cells express latency-associated peptide and inhibit T cell activation in a TGF-beta-dependent manner. PG - 4017-21 AB - Dendritic cells (DCs) play a critical role in both initiating immune responses and in maintaining peripheral tolerance. However, the exact mechanism by which DCs instruct/influence the generation of effector vs regulatory T cells is not clear. In this study, we present evidence that TGF-beta, an important immunoregulatory molecule, is present on the surface of ex vivo immature human DCs bound by latency-associated peptide (LAP). Maturation of DCs upon stimulation with LPS results in loss of membrane-bound LAP and up-regulation of HLA class II and costimulatory molecules. The presence of LAP on immature DCs selectively inhibits Th1 cell but not Th17 cell differentiation and is required for differentiation and/or survival of Foxp3-positive regulatory T cells. Taken together, our results indicate that surface expression of TGF-beta on DCs in association with LAP is one of the mechanisms by which immature DCs limit T cell activation and thus prevent autoimmune responses. FAU - Gandhi, Roopali AU - Gandhi R AD - Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. FAU - Anderson, David E AU - Anderson DE FAU - Weiner, Howard L AU - Weiner HL LA - eng GR - NS 23132/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Antibodies) RN - 0 (FOXP3 protein, human) RN - 0 (Forkhead Transcription Factors) RN - 0 (Lipopolysaccharides) RN - 0 (RNA, Small Interfering) RN - 0 (Transforming Growth Factor beta) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Antibodies/pharmacology MH - Autoimmunity MH - Cell Differentiation MH - Cell Polarity MH - Cell Proliferation MH - Coculture Techniques MH - Dendritic Cells/chemistry/drug effects/*immunology MH - Forkhead Transcription Factors/analysis/metabolism MH - Humans MH - Interferon-gamma/metabolism MH - Lipopolysaccharides/pharmacology MH - Lymphocyte Activation MH - RNA, Small Interfering/genetics MH - T-Lymphocytes/*immunology MH - T-Lymphocytes, Regulatory/immunology MH - Th1 Cells/immunology MH - Transforming Growth Factor beta/analysis/antagonists & inhibitors/*metabolism EDAT- 2007/03/21 09:00 MHDA- 2007/06/20 09:00 CRDT- 2007/03/21 09:00 PHST- 2007/03/21 09:00 [pubmed] PHST- 2007/06/20 09:00 [medline] PHST- 2007/03/21 09:00 [entrez] AID - 178/7/4017 [pii] AID - 10.4049/jimmunol.178.7.4017 [doi] PST - ppublish SO - J Immunol. 2007 Apr 1;178(7):4017-21. doi: 10.4049/jimmunol.178.7.4017.