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10.1038/s41598-020-62480-3 http://scihub22266oqcxt.onion/10.1038/s41598-020-62480-3 32245990!7125190!32245990     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=32245990&cmd=llinks): Failed to open stream: HTTP request failed! 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Native/citrullinated LL37-specific T-cells help autoantibody production in Systemic Lupus Erythematosus |pdf=|usr=}}{{32245990}} gab.com Text Native/citrullinated LL37-specific T-cells help autoantibody production in Systemic Lupus Erythematosus JO: Sci Rep http://www.kidney.de/pget.php?&tw=1&pmid=32245990 #FOAvip LL37 exerts a dual pathogenic role in psoriasis. Bound to self-DNA/RNA, LL37 licenses autoreactivity by stimulating plasmacytoid dendritic cells-(pDCs)-Type I interferon (IFN-I) and acts as autoantigen for pathogenic Th17-cells. In systemic lupus erythematosus (SLE), LL37 also triggers IFN-I in pDCs and is target of pathogenic autoantibodies. However, whether LL37 activates T-cells in SLE and how the latter differ from psoriasis LL37-specific T-cells is unknown. Here we found that 45% SLE patients had circulating T-cells strongly responding to LL37, which correlate with anti-LL37 antibodies/disease activity. In contrast to psoriatic Th17-cells, these LL37-specific SLE T-cells displayed a T-follicular helper-(T(FH))-like phenotype, with CXCR5/Bcl-6 and IL-21 expression, implicating a role in stimulation of pathogenic autoantibodies. Accordingly, SLE LL37-specific T-cells promoted B-cell secretion of pathogenic anti-LL37 antibodies in vitro. Importantly, we identified abundant citrullinated LL37 (cit-LL37) in SLE tissues (skin and kidney) and observed very pronounced reactivity of LL37-specific SLE T-cells to cit-LL37, compared to native-LL37, which was much more occasional in psoriasis. Thus, in SLE, we identified LL37-specific T-cells with a distinct functional specialization and antigenic specificity. This suggests that autoantigenic specificity is independent from the nature of the autoantigen, but rather relies on the disease-specific milieu driving T-cell subset polarization and autoantigen modifications. Twit Text FOAVip Native/citrullinated LL37-specific T-cells help autoantibody production in Systemic Lupus Erythematosus ????Sci Rep http://www.kidney.de/pget.php?&tw=1&pmid=32245990 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=32245990 #FOAvip English Wikipedia <ref>{{Cite pmid|32245990}}</ref> Native/citrullinated LL37-specific T-cells help autoantibody production in Systemic Lupus Erythematosus #MMPMID32245990 Lande R; Palazzo R; Gestermann N; Jandus C; Falchi M; Spadaro F; Riccieri V; James EA; Butera A; Boirivant M; Feldmeyer L; Surbeck I; Di Lucca J; Stuber F; Spinelli FR; Botti E; Marinari B; Bianchi L; Pica R; Cerbelli B; Giannakakis K; Auteri SE; Daniels I; Durrant LG; Horstman S; Costanzo A; Romero P; Alessandri C; Conti F; Valesini G; Gilliet M; Chizzolini C; Frasca L Sci Rep 2020[Apr]; 10 (1): 5851 PMID32245990show ga LL37 exerts a dual pathogenic role in psoriasis. Bound to self-DNA/RNA, LL37 licenses autoreactivity by stimulating plasmacytoid dendritic cells-(pDCs)-Type I interferon (IFN-I) and acts as autoantigen for pathogenic Th17-cells. In systemic lupus erythematosus (SLE), LL37 also triggers IFN-I in pDCs and is target of pathogenic autoantibodies. However, whether LL37 activates T-cells in SLE and how the latter differ from psoriasis LL37-specific T-cells is unknown. Here we found that 45% SLE patients had circulating T-cells strongly responding to LL37, which correlate with anti-LL37 antibodies/disease activity. In contrast to psoriatic Th17-cells, these LL37-specific SLE T-cells displayed a T-follicular helper-(T(FH))-like phenotype, with CXCR5/Bcl-6 and IL-21 expression, implicating a role in stimulation of pathogenic autoantibodies. Accordingly, SLE LL37-specific T-cells promoted B-cell secretion of pathogenic anti-LL37 antibodies in vitro. Importantly, we identified abundant citrullinated LL37 (cit-LL37) in SLE tissues (skin and kidney) and observed very pronounced reactivity of LL37-specific SLE T-cells to cit-LL37, compared to native-LL37, which was much more occasional in psoriasis. Thus, in SLE, we identified LL37-specific T-cells with a distinct functional specialization and antigenic specificity. This suggests that autoantigenic specificity is independent from the nature of the autoantigen, but rather relies on the disease-specific milieu driving T-cell subset polarization and autoantigen modifications. |Anti-Citrullinated Protein Antibodies/immunology[MESH] |Antibodies, Antinuclear/immunology[MESH] |Antibody Formation/immunology[MESH] |Antimicrobial Cationic Peptides/*immunology[MESH] |Autoantibodies/*immunology[MESH] |Cathelicidins[MESH] |DNA/immunology[MESH] |Dendritic Cells/immunology[MESH] |Female[MESH] |Humans[MESH] |Lupus Erythematosus, Systemic/etiology/*immunology[MESH] |Male[MESH] |Psoriasis/etiology/immunology[MESH] |T-Lymphocytes/*immunology[MESH]Native/citrullinated LL37-specific T-cells help autoantibody productio(epmc).pdf DeepDyve Pubget Overpricing