PMID- 17675476 OWN - NLM STAT- MEDLINE DCOM- 20071003 LR - 20190516 IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 179 IP - 4 DP - 2007 Aug 15 TI - Selective expansion of foxp3-positive regulatory T cells and immunosuppression by suppressors of cytokine signaling 3-deficient dendritic cells. PG - 2170-9 AB - Dendritic cells (DCs) induce immunity and immunological tolerance as APCs. It has been shown that DCs secreting IL-10 induce IL-10(+) Tr1-type regulatory T (Treg) cells, whereas Foxp3-positive Treg cells are expanded from naive CD4(+) T cells by coculturing with mature DCs. However, the regulatory mechanism of expansion of Foxp3(+) Treg cells by DCs has not been clarified. In this study, we demonstrated that suppressors of cytokine signaling (SOCS)-3-deficient DCs have a strong potential as Foxp3(+) T cell-inducing tolerogenic DCs. SOCS3(-/-) DCs expressed lower levels of class II MHC, CD40, CD86, and IL-12 than wild-type (WT)-DCs both in vitro and in vivo, and showed constitutive activation of STAT3. Foxp3(-) effector T cells were predominantly expanded by the priming with WT-DCs, whereas Foxp3(+) Treg cells were selectively expanded by SOCS3(-/-) DCs. Adoptive transfer of SOCS3(-/-) DCs reduced the severity of experimental autoimmune encephalomyelitis. Foxp3(+) T cell expansion was blocked by anti-TGF-beta Ab, and SOCS3(-/-) DCs produced higher levels of TGF-beta than WT-DCs, suggesting that TGF-beta plays an essential role in the expansion of Foxp3(+) Treg cells. These results indicate an important role of SOCS3 in determining on immunity or tolerance by DCs. FAU - Matsumura, Yumiko AU - Matsumura Y AD - Division of Molecular and Cellular Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan. FAU - Kobayashi, Takashi AU - Kobayashi T FAU - Ichiyama, Kenji AU - Ichiyama K FAU - Yoshida, Ryoko AU - Yoshida R FAU - Hashimoto, Masayuki AU - Hashimoto M FAU - Takimoto, Tomohito AU - Takimoto T FAU - Tanaka, Kentaro AU - Tanaka K FAU - Chinen, Takatoshi AU - Chinen T FAU - Shichita, Takashi AU - Shichita T FAU - Wyss-Coray, Tony AU - Wyss-Coray T FAU - Sato, Katsuaki AU - Sato K FAU - Yoshimura, Akihiko AU - Yoshimura A 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 (Antibodies) RN - 0 (B7-2 Antigen) RN - 0 (CD40 Antigens) RN - 0 (Cd86 protein, mouse) RN - 0 (Forkhead Transcription Factors) RN - 0 (Foxp3 protein, mouse) RN - 0 (Histocompatibility Antigens Class II) RN - 0 (Socs3 protein, mouse) RN - 0 (Suppressor of Cytokine Signaling 3 Protein) RN - 0 (Suppressor of Cytokine Signaling Proteins) RN - 0 (Transforming Growth Factor beta) RN - 130068-27-8 (Interleukin-10) RN - 187348-17-0 (Interleukin-12) SB - IM MH - Adoptive Transfer MH - Animals MH - Antibodies/immunology/pharmacology MH - B7-2 Antigen/genetics/immunology MH - CD40 Antigens/genetics/immunology MH - *Cell Proliferation MH - Coculture Techniques MH - Dendritic Cells/*immunology MH - Forkhead Transcription Factors/genetics/*immunology MH - Histocompatibility Antigens Class II/genetics/immunology MH - Immune Tolerance/drug effects/genetics/*immunology MH - Interleukin-10/genetics/immunology MH - Interleukin-12/genetics/immunology MH - Mice MH - Mice, Knockout MH - Suppressor of Cytokine Signaling 3 Protein MH - Suppressor of Cytokine Signaling Proteins/deficiency/*immunology MH - T-Lymphocytes, Regulatory/*immunology MH - Transforming Growth Factor beta/genetics/immunology EDAT- 2007/08/07 09:00 MHDA- 2007/10/04 09:00 CRDT- 2007/08/07 09:00 PHST- 2007/08/07 09:00 [pubmed] PHST- 2007/10/04 09:00 [medline] PHST- 2007/08/07 09:00 [entrez] AID - 179/4/2170 [pii] AID - 10.4049/jimmunol.179.4.2170 [doi] PST - ppublish SO - J Immunol. 2007 Aug 15;179(4):2170-9. doi: 10.4049/jimmunol.179.4.2170.