Activation of gp130 signaling in T cells drives T < sub > H < /sub > 17-mediated multi-organ autoimmunity
Sci Signal. 2024 Feb 20;17(824):eadc9662. doi: 10.1126/scisignal.adc9662. Epub 2024 Feb 20.ABSTRACTThe IL-6-gp130-STAT3 signaling axis is a major regulator of inflammation. Activating mutations in the gene encoding gp130 and germline gain-of-function mutations in STAT3 (STAT3GOF) are associated with multi-organ autoimmunity, severe morbidity, and adverse prognosis. To dissect crucial cellular subsets and disease biology involved in activated gp130 signaling, the gp130-JAK-STAT3 axis was constitutively activated using a transgene, L-gp130, specifically targeted to T cells. Activating gp130 signaling in T cells in vivo resul...
Source: Science Signaling - February 20, 2024 Category: Biomedical Science Authors: Francis Baumgartner Stefanos A Bamopoulos Laura Faletti Hsiang-Jung Hsiao Maximilian Holz Irene Gonzalez-Menendez Lloren ç Boldo Arik Horne Sanket Gosavi Ceren Özerdem Nikita Singh Sven Liebig Senthilkumar Ramamoorthy Malte Lehmann Uta Demel Anja A K ü Source Type: research
Poachers turned gamekeepers in T cells
Sci Signal. 2024 Feb 20;17(824):eado6463. doi: 10.1126/scisignal.ado6463. Epub 2024 Feb 20.ABSTRACTThe efficacy of therapeutic T cells is enhanced by incorporating mutations associated with autoimmunity or lymphoma.PMID:38377178 | DOI:10.1126/scisignal.ado6463 (Source: Science Signaling)
Source: Science Signaling - February 20, 2024 Category: Biomedical Science Authors: John F Foley Source Type: research
Designer high-density lipoprotein particles enhance endothelial barrier function and suppress inflammation
Sci Signal. 2024 Feb 20;17(824):eadg9256. doi: 10.1126/scisignal.adg9256. Epub 2024 Feb 20.ABSTRACTHigh-density lipoprotein (HDL) nanoparticles promote endothelial cell (EC) function and suppress inflammation, but their utility in treating EC dysfunction has not been fully explored. Here, we describe a fusion protein named ApoA1-ApoM (A1M) consisting of apolipoprotein A1 (ApoA1), the principal structural protein of HDL that forms lipid nanoparticles, and ApoM, a chaperone for the bioactive lipid sphingosine 1-phosphate (S1P). A1M forms HDL-like particles, binds to S1P, and is signaling competent. Molecular dynamics simulat...
Source: Science Signaling - February 20, 2024 Category: Biomedical Science Authors: Yueh-Chien Lin Steven Swendeman Irina S Moreira Avishek Ghosh Andrew Kuo N ícia Rosário-Ferreira Shihui Guo Alan Culbertson Michel V Levesque Andreane Cartier Takahiro Seno Alec Schmaier Sylvain Galvani Asuka Inoue Samir M Parikh Garret A FitzGerald Dav Source Type: research
Activation of gp130 signaling in T cells drives T < sub > H < /sub > 17-mediated multi-organ autoimmunity
Sci Signal. 2024 Feb 20;17(824):eadc9662. doi: 10.1126/scisignal.adc9662. Epub 2024 Feb 20.ABSTRACTThe IL-6-gp130-STAT3 signaling axis is a major regulator of inflammation. Activating mutations in the gene encoding gp130 and germline gain-of-function mutations in STAT3 (STAT3GOF) are associated with multi-organ autoimmunity, severe morbidity, and adverse prognosis. To dissect crucial cellular subsets and disease biology involved in activated gp130 signaling, the gp130-JAK-STAT3 axis was constitutively activated using a transgene, L-gp130, specifically targeted to T cells. Activating gp130 signaling in T cells in vivo resul...
Source: Science Signaling - February 20, 2024 Category: Biomedical Science Authors: Francis Baumgartner Stefanos A Bamopoulos Laura Faletti Hsiang-Jung Hsiao Maximilian Holz Irene Gonzalez-Menendez Lloren ç Boldo Arik Horne Sanket Gosavi Ceren Özerdem Nikita Singh Sven Liebig Senthilkumar Ramamoorthy Malte Lehmann Uta Demel Anja A K ü Source Type: research
Poachers turned gamekeepers in T cells
Sci Signal. 2024 Feb 20;17(824):eado6463. doi: 10.1126/scisignal.ado6463. Epub 2024 Feb 20.ABSTRACTThe efficacy of therapeutic T cells is enhanced by incorporating mutations associated with autoimmunity or lymphoma.PMID:38377178 | DOI:10.1126/scisignal.ado6463 (Source: Science Signaling)
Source: Science Signaling - February 20, 2024 Category: Biomedical Science Authors: John F Foley Source Type: research
Designer high-density lipoprotein particles enhance endothelial barrier function and suppress inflammation
Sci Signal. 2024 Feb 20;17(824):eadg9256. doi: 10.1126/scisignal.adg9256. Epub 2024 Feb 20.ABSTRACTHigh-density lipoprotein (HDL) nanoparticles promote endothelial cell (EC) function and suppress inflammation, but their utility in treating EC dysfunction has not been fully explored. Here, we describe a fusion protein named ApoA1-ApoM (A1M) consisting of apolipoprotein A1 (ApoA1), the principal structural protein of HDL that forms lipid nanoparticles, and ApoM, a chaperone for the bioactive lipid sphingosine 1-phosphate (S1P). A1M forms HDL-like particles, binds to S1P, and is signaling competent. Molecular dynamics simulat...
Source: Science Signaling - February 20, 2024 Category: Biomedical Science Authors: Yueh-Chien Lin Steven Swendeman Irina S Moreira Avishek Ghosh Andrew Kuo N ícia Rosário-Ferreira Shihui Guo Alan Culbertson Michel V Levesque Andreane Cartier Takahiro Seno Alec Schmaier Sylvain Galvani Asuka Inoue Samir M Parikh Garret A FitzGerald Dav Source Type: research
Activation of gp130 signaling in T cells drives T < sub > H < /sub > 17-mediated multi-organ autoimmunity
Sci Signal. 2024 Feb 20;17(824):eadc9662. doi: 10.1126/scisignal.adc9662. Epub 2024 Feb 20.ABSTRACTThe IL-6-gp130-STAT3 signaling axis is a major regulator of inflammation. Activating mutations in the gene encoding gp130 and germline gain-of-function mutations in STAT3 (STAT3GOF) are associated with multi-organ autoimmunity, severe morbidity, and adverse prognosis. To dissect crucial cellular subsets and disease biology involved in activated gp130 signaling, the gp130-JAK-STAT3 axis was constitutively activated using a transgene, L-gp130, specifically targeted to T cells. Activating gp130 signaling in T cells in vivo resul...
Source: Science Signaling - February 20, 2024 Category: Biomedical Science Authors: Francis Baumgartner Stefanos A Bamopoulos Laura Faletti Hsiang-Jung Hsiao Maximilian Holz Irene Gonzalez-Menendez Lloren ç Boldo Arik Horne Sanket Gosavi Ceren Özerdem Nikita Singh Sven Liebig Senthilkumar Ramamoorthy Malte Lehmann Uta Demel Anja A K ü Source Type: research
Poachers turned gamekeepers in T cells
Sci Signal. 2024 Feb 20;17(824):eado6463. doi: 10.1126/scisignal.ado6463. Epub 2024 Feb 20.ABSTRACTThe efficacy of therapeutic T cells is enhanced by incorporating mutations associated with autoimmunity or lymphoma.PMID:38377178 | DOI:10.1126/scisignal.ado6463 (Source: Science Signaling)
Source: Science Signaling - February 20, 2024 Category: Biomedical Science Authors: John F Foley Source Type: research
Designer high-density lipoprotein particles enhance endothelial barrier function and suppress inflammation
Sci Signal. 2024 Feb 20;17(824):eadg9256. doi: 10.1126/scisignal.adg9256. Epub 2024 Feb 20.ABSTRACTHigh-density lipoprotein (HDL) nanoparticles promote endothelial cell (EC) function and suppress inflammation, but their utility in treating EC dysfunction has not been fully explored. Here, we describe a fusion protein named ApoA1-ApoM (A1M) consisting of apolipoprotein A1 (ApoA1), the principal structural protein of HDL that forms lipid nanoparticles, and ApoM, a chaperone for the bioactive lipid sphingosine 1-phosphate (S1P). A1M forms HDL-like particles, binds to S1P, and is signaling competent. Molecular dynamics simulat...
Source: Science Signaling - February 20, 2024 Category: Biomedical Science Authors: Yueh-Chien Lin Steven Swendeman Irina S Moreira Avishek Ghosh Andrew Kuo N ícia Rosário-Ferreira Shihui Guo Alan Culbertson Michel V Levesque Andreane Cartier Takahiro Seno Alec Schmaier Sylvain Galvani Asuka Inoue Samir M Parikh Garret A FitzGerald Dav Source Type: research
GPCR kinases differentially modulate biased signaling downstream of CXCR3 depending on their subcellular localization
Sci Signal. 2024 Feb 13;17(823):eadd9139. doi: 10.1126/scisignal.add9139. Epub 2024 Feb 13.ABSTRACTSome G protein-coupled receptors (GPCRs) demonstrate biased signaling such that ligands of the same receptor exclusively or preferentially activate certain downstream signaling pathways over others. This phenomenon may result from ligand-specific receptor phosphorylation by GPCR kinases (GRKs). GPCR signaling can also exhibit location bias because GPCRs traffic to and signal from subcellular compartments in addition to the plasma membrane. Here, we investigated whether GRKs contributed to location bias in GPCR signaling. GRKs...
Source: Science Signaling - February 13, 2024 Category: Biomedical Science Authors: Julia Gardner Dylan Scott Eiger Chloe Hicks Issac Choi Uyen Pham Anand Chundi Ojas Namjoshi Sudarshan Rajagopal Source Type: research
RNAs create a sticky situation
Sci Signal. 2024 Feb 13;17(823):eado4078. doi: 10.1126/scisignal.ado4078. Epub 2024 Feb 13.ABSTRACTGlycated RNAs on neutrophils enable adhesion to the endothelium and extravasation to sites of inflammation.PMID:38349967 | DOI:10.1126/scisignal.ado4078 (Source: Science Signaling)
Source: Science Signaling - February 13, 2024 Category: Biomedical Science Authors: Wei Wong Source Type: research
Mechanisms of biased agonism by G α < sub > i/o < /sub > -biased stapled peptide agonists of the relaxin-3 receptor
Sci Signal. 2024 Feb 13;17(823):eabl5880. doi: 10.1126/scisignal.abl5880. Epub 2024 Feb 13.ABSTRACTThe neuropeptide relaxin-3 is composed of an A chain and a B chain held together by disulfide bonds, and it modulates functions such as anxiety and food intake by binding to and activating its cognate receptor RXFP3, mainly through the B chain. Biased ligands of RXFP3 would help to determine the molecular mechanisms underlying the activation of G proteins and β-arrestins downstream of RXFP3 that lead to such diverse functions. We showed that the i, i+4 stapled relaxin-3 B chains, 14s18 and d(1-7)14s18, were Gαi/o-biased ago...
Source: Science Signaling - February 13, 2024 Category: Biomedical Science Authors: Tharindunee Jayakody Asuka Inoue Srinivasaraghavan Kannan Gaku Nakamura Kouki Kawakami Krishan Mendis Thanh-Binh Nguyen Jianguo Li Deron R Herr Chandra S Verma Gavin S Dawe Source Type: research
GPCR kinases differentially modulate biased signaling downstream of CXCR3 depending on their subcellular localization
Sci Signal. 2024 Feb 13;17(823):eadd9139. doi: 10.1126/scisignal.add9139. Epub 2024 Feb 13.ABSTRACTSome G protein-coupled receptors (GPCRs) demonstrate biased signaling such that ligands of the same receptor exclusively or preferentially activate certain downstream signaling pathways over others. This phenomenon may result from ligand-specific receptor phosphorylation by GPCR kinases (GRKs). GPCR signaling can also exhibit location bias because GPCRs traffic to and signal from subcellular compartments in addition to the plasma membrane. Here, we investigated whether GRKs contributed to location bias in GPCR signaling. GRKs...
Source: Science Signaling - February 13, 2024 Category: Biomedical Science Authors: Julia Gardner Dylan Scott Eiger Chloe Hicks Issac Choi Uyen Pham Anand Chundi Ojas Namjoshi Sudarshan Rajagopal Source Type: research
RNAs create a sticky situation
Sci Signal. 2024 Feb 13;17(823):eado4078. doi: 10.1126/scisignal.ado4078. Epub 2024 Feb 13.ABSTRACTGlycated RNAs on neutrophils enable adhesion to the endothelium and extravasation to sites of inflammation.PMID:38349967 | DOI:10.1126/scisignal.ado4078 (Source: Science Signaling)
Source: Science Signaling - February 13, 2024 Category: Biomedical Science Authors: Wei Wong Source Type: research
Mechanisms of biased agonism by G α < sub > i/o < /sub > -biased stapled peptide agonists of the relaxin-3 receptor
Sci Signal. 2024 Feb 13;17(823):eabl5880. doi: 10.1126/scisignal.abl5880. Epub 2024 Feb 13.ABSTRACTThe neuropeptide relaxin-3 is composed of an A chain and a B chain held together by disulfide bonds, and it modulates functions such as anxiety and food intake by binding to and activating its cognate receptor RXFP3, mainly through the B chain. Biased ligands of RXFP3 would help to determine the molecular mechanisms underlying the activation of G proteins and β-arrestins downstream of RXFP3 that lead to such diverse functions. We showed that the i, i+4 stapled relaxin-3 B chains, 14s18 and d(1-7)14s18, were Gαi/o-biased ago...
Source: Science Signaling - February 13, 2024 Category: Biomedical Science Authors: Tharindunee Jayakody Asuka Inoue Srinivasaraghavan Kannan Gaku Nakamura Kouki Kawakami Krishan Mendis Thanh-Binh Nguyen Jianguo Li Deron R Herr Chandra S Verma Gavin S Dawe Source Type: research
