PubMed:20131264 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/20131264","sourcedb":"PubMed","sourceid":"20131264","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/20131264","text":"Interleukin-23 promotes Th17 differentiation by inhibiting T-bet and FoxP3 and is required for elevation of interleukin-22, but not interleukin-21, in autoimmune experimental arthritis.\nOBJECTIVE: To examine the role of interleukin-23 (IL-23) in subgroup polarization of IL-17A-positive and/or interferon-gamma (IFNgamma)-positive T cells in autoimmune disease-prone DBA/1 mice with and without collagen-induced arthritis.\nMETHODS: A magnetic-activated cell sorting system was used to isolate CD4+ T cells from the spleen of naive and type II collagen (CII)-immunized DBA/1 mice. These CD4+ T cells were stimulated in vitro under Th0, Th1, or different Th17 culture conditions. Intracellular staining for IL-17A and IFNgamma was evaluated by flow cytometry. In addition, Th17 cytokines and T helper-specific transcription factors were analyzed by enzyme-linked immunosorbent assay and/or quantitative polymerase chain reaction.\nRESULTS: In CD4+ T cells from naive DBA/1 mice, IL-23 alone hardly induced retinoic acid-related orphan receptor gammat (RORgammat), Th17 polarization, and Th17 cytokines, but it inhibited T-bet expression. In contrast, transforming growth factor beta1 (TGFbeta1)/IL-6 was a potent inducer of RORgammat, RORalpha, IL-17A, IL-17F, IL-21, and FoxP3 in these cells. In contrast to TGFbeta1/IL-6, IL-23 was critical for the induction of IL-22 in CD4+ T cells from both naive and CII-immunized DBA/1 mice. Consistent with these findings, IL-23 showed a more pronounced induction of the IL-17A+IFNgamma- subset in CD4+ T cells from CII-immunized mice. However, in CD4+ T cells from naive mice, IL-23 significantly increased the TGFbeta1/IL-6-induced Th17 polarization, including elevated levels of IL-17A and IL-17F and decreased expression of T-bet and FoxP3. Of note, the IL-23-induced increase in IL-17A and IL-17F levels was prevented in T-bet-deficient mice.\nCONCLUSION: IL-23 promotes Th17 differentiation by inhibiting T-bet and FoxP3 and is required for elevation of IL-22, but not IL-21, levels in autoimmune arthritis. These data indicate different mechanisms for IL-23 and TGFbeta1/IL-6 at the transcription factor level during Th17 differentiation in autoimmune experimental arthritis.","tracks":[{"project":"Allie","denotations":[{"id":"SS1_20131264_2_0","span":{"begin":220,"end":234},"obj":"expanded"},{"id":"SS2_20131264_2_0","span":{"begin":236,"end":241},"obj":"abbr"},{"id":"SS1_20131264_2_1","span":{"begin":294,"end":310},"obj":"expanded"},{"id":"SS2_20131264_2_1","span":{"begin":312,"end":320},"obj":"abbr"},{"id":"SS1_20131264_4_0","span":{"begin":500,"end":551},"obj":"expanded"},{"id":"SS2_20131264_4_0","span":{"begin":553,"end":556},"obj":"abbr"},{"id":"SS1_20131264_9_0","span":{"begin":1012,"end":1047},"obj":"expanded"},{"id":"SS2_20131264_9_0","span":{"begin":1049,"end":1058},"obj":"abbr"},{"id":"SS1_20131264_10_0","span":{"begin":1148,"end":1180},"obj":"expanded"},{"id":"SS2_20131264_10_0","span":{"begin":1182,"end":1190},"obj":"abbr"}],"relations":[{"id":"AE1_20131264_2_0","pred":"abbreviatedTo","subj":"SS1_20131264_2_0","obj":"SS2_20131264_2_0"},{"id":"AE1_20131264_2_1","pred":"abbreviatedTo","subj":"SS1_20131264_2_1","obj":"SS2_20131264_2_1"},{"id":"AE1_20131264_4_0","pred":"abbreviatedTo","subj":"SS1_20131264_4_0","obj":"SS2_20131264_4_0"},{"id":"AE1_20131264_9_0","pred":"abbreviatedTo","subj":"SS1_20131264_9_0","obj":"SS2_20131264_9_0"},{"id":"AE1_20131264_10_0","pred":"abbreviatedTo","subj":"SS1_20131264_10_0","obj":"SS2_20131264_10_0"}],"attributes":[{"subj":"SS1_20131264_2_0","pred":"source","obj":"Allie"},{"subj":"SS2_20131264_2_0","pred":"source","obj":"Allie"},{"subj":"SS1_20131264_2_1","pred":"source","obj":"Allie"},{"subj":"SS2_20131264_2_1","pred":"source","obj":"Allie"},{"subj":"SS1_20131264_4_0","pred":"source","obj":"Allie"},{"subj":"SS2_20131264_4_0","pred":"source","obj":"Allie"},{"subj":"SS1_20131264_9_0","pred":"source","obj":"Allie"},{"subj":"SS2_20131264_9_0","pred":"source","obj":"Allie"},{"subj":"SS1_20131264_10_0","pred":"source","obj":"Allie"},{"subj":"SS2_20131264_10_0","pred":"source","obj":"Allie"}]},{"project":"2015-BEL-Sample-2","denotations":[{"id":"BEL:20034538","span":{"begin":1574,"end":1884},"obj":"complex(p(MGI:Il12b),p(MGI:Il23a)) decreases r(MGI:Foxp3)"},{"id":"BEL:20034542","span":{"begin":1574,"end":1884},"obj":"complex(p(MGI:Il12b),p(MGI:Il23a)) increases r(MGI:Il17a)"},{"id":"BEL:20034546","span":{"begin":1574,"end":1884},"obj":"complex(p(MGI:Il12b),p(MGI:Il23a)) increases r(MGI:Il17f)"},{"id":"BEL:20034550","span":{"begin":1291,"end":1427},"obj":"complex(p(MGI:Il12b),p(MGI:Il23a)) increases r(MGI:Il22)"},{"id":"BEL:20034564","span":{"begin":935,"end":1133},"obj":"complex(p(MGI:Il23a),p(MGI:Il1b)) decreases r(MGI:Tbx21)"}],"attributes":[{"subj":"BEL:20034538","pred":"source","obj":"2015-BEL-Sample-2"},{"subj":"BEL:20034542","pred":"source","obj":"2015-BEL-Sample-2"},{"subj":"BEL:20034546","pred":"source","obj":"2015-BEL-Sample-2"},{"subj":"BEL:20034550","pred":"source","obj":"2015-BEL-Sample-2"},{"subj":"BEL:20034564","pred":"source","obj":"2015-BEL-Sample-2"}]},{"project":"PubmedHPO","denotations":[{"id":"T1","span":{"begin":342,"end":360},"obj":"HP_0002960"},{"id":"T2","span":{"begin":342,"end":352},"obj":"HP_0002960"},{"id":"T3","span":{"begin":412,"end":421},"obj":"HP_0001369"}],"attributes":[{"subj":"T1","pred":"source","obj":"PubmedHPO"},{"subj":"T2","pred":"source","obj":"PubmedHPO"},{"subj":"T3","pred":"source","obj":"PubmedHPO"}]},{"project":"PubMed_Structured_Abstracts","denotations":[{"id":"T1","span":{"begin":197,"end":422},"obj":"OBJECTIVE"},{"id":"T2","span":{"begin":432,"end":927},"obj":"METHODS"},{"id":"T3","span":{"begin":937,"end":1885},"obj":"RESULTS"},{"id":"T4","span":{"begin":1898,"end":2219},"obj":"CONCLUSIONS"}],"attributes":[{"subj":"T1","pred":"source","obj":"PubMed_Structured_Abstracts"},{"subj":"T2","pred":"source","obj":"PubMed_Structured_Abstracts"},{"subj":"T3","pred":"source","obj":"PubMed_Structured_Abstracts"},{"subj":"T4","pred":"source","obj":"PubMed_Structured_Abstracts"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"Allie","color":"#eca093","default":true},{"id":"2015-BEL-Sample-2","color":"#939fec"},{"id":"PubmedHPO","color":"#b9ec93"},{"id":"PubMed_Structured_Abstracts","color":"#ec93d3"}]}]}}