PMID- 15712252 OWN - NLM STAT- MEDLINE DCOM- 20050916 LR - 20171116 IS - 1099-498X (Print) IS - 1099-498X (Linking) VI - 7 IP - 7 DP - 2005 Jul TI - Cytokine production by dendritic cells genetically engineered to express IL-4: induction of Th2 responses and differential regulation of IL-12 and IL-23 synthesis. PG - 869-77 AB - Dendritic cells (DCs) retrovirally transduced with IL-4 have recently been shown to inhibit murine collagen-induced arthritis and associated Th1 immune responses in vivo, but the mechanisms that underly these effects are not yet understood. In this report we demonstrate that IL-4-transduced DCs loaded with antigen led to lower T cell production of IFN-gamma, increased production of IL-4, and an attenuated, delayed type hypersensitivity response. We hypothesized that the ability of such DCs to regulate the Th1 immune response in vivo depends in part on their capacity to produce IL-12 and IL-23. Quantitative mRNA analysis revealed that IL-4-transduced DCs stimulated with CD40 ligand expressed higher levels of IL-12p35 mRNA, but lower levels of mRNA for IL-23p19 and the common subunit p40 found in both IL-12 and IL-23, compared with control DCs. These results, which indicate that expression of the IL-12 and IL-23 subunits is differentially regulated in IL-4-transduced DCs, were confirmed by ELISA of the IL-12 and IL-23 heterodimers. Thus, therapeutic suppression of Th1 -mediated autoimmunity (as recently shown in murine collagen-induced arthritis) and induction of Th2 responses in vivo by IL-4-transduced DCs occurs despite their potential to produce increased levels of IL-12, but could reflect, in part, decreased production of IL-23. CI - Copyright 2005 John Wiley & Sons, Ltd. FAU - Morita, Yoshitaka AU - Morita Y AD - Division of Nephrology and Rheumatology, Department of Internal Medicine, Kawasaki Medical School, Kurashiki, Japan. FAU - Gupta, Raj AU - Gupta R FAU - Seidl, Kelly M AU - Seidl KM FAU - McDonagh, Kevin T AU - McDonagh KT FAU - Fox, David A AU - Fox DA LA - eng GR - AR38477/AR/NIAMS NIH HHS/United States GR - DK02349/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - England TA - J Gene Med JT - The journal of gene medicine JID - 9815764 RN - 0 (Cytokines) RN - 0 (Il23a protein, mouse) RN - 0 (Interleukin-23) RN - 0 (Interleukin-23 Subunit p19) RN - 0 (Interleukins) RN - 147205-72-9 (CD40 Ligand) RN - 187348-17-0 (Interleukin-12) RN - 207137-56-2 (Interleukin-4) RN - 9013-72-3 (Hemocyanins) RN - FV4Y0JO2CX (keyhole-limpet hemocyanin) SB - IM MH - Animals MH - Bone Marrow Cells MH - CD40 Ligand/genetics MH - Cytokines/biosynthesis/*immunology MH - Dendritic Cells/*immunology/metabolism MH - *Gene Transfer Techniques MH - Hemocyanins/immunology MH - Interleukin-12/*biosynthesis/metabolism MH - Interleukin-23 MH - Interleukin-23 Subunit p19 MH - Interleukin-4/*genetics/immunology MH - Interleukins/*biosynthesis/metabolism MH - Male MH - Mice MH - Mice, Inbred C57BL MH - NIH 3T3 Cells MH - Th2 Cells/*immunology/metabolism MH - Transfection EDAT- 2005/02/16 09:00 MHDA- 2005/09/17 09:00 CRDT- 2005/02/16 09:00 PHST- 2005/02/16 09:00 [pubmed] PHST- 2005/09/17 09:00 [medline] PHST- 2005/02/16 09:00 [entrez] AID - 10.1002/jgm.730 [doi] PST - ppublish SO - J Gene Med. 2005 Jul;7(7):869-77. doi: 10.1002/jgm.730.