BAFF Promotes Th17 Cells and Aggravates Experimental Autoimmune Encephalomyelitis
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{"title"=>"BAFF promotes Th17 cells and aggravates experimental autoimmune encephalomyelitis", "type"=>"journal", "authors"=>[{"first_name"=>"Xiaohui", "last_name"=>"Zhou", "scopus_author_id"=>"56332617600"}, {"first_name"=>"Zanxian", "last_name"=>"Xia", "scopus_author_id"=>"56714586800"}, {"first_name"=>"Qin", "last_name"=>"Lan", "scopus_author_id"=>"49561357900"}, {"first_name"=>"Julie", "last_name"=>"Wang", "scopus_author_id"=>"36083699300"}, {"first_name"=>"Wenru", "last_name"=>"Su", "scopus_author_id"=>"37035267600"}, {"first_name"=>"Yuan Ping", "last_name"=>"Han", "scopus_author_id"=>"7404096288"}, {"first_name"=>"Huimin", "last_name"=>"Fan", "scopus_author_id"=>"14037153100"}, {"first_name"=>"Zhongmin", "last_name"=>"Liu", "scopus_author_id"=>"35318039400"}, {"first_name"=>"William", "last_name"=>"Stohl", "scopus_author_id"=>"7005917493"}, {"first_name"=>"Song Guo", "last_name"=>"Zheng", "scopus_author_id"=>"7403146499"}], "year"=>2011, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "pmid"=>"21897850", "scopus"=>"2-s2.0-80052293917", "doi"=>"10.1371/journal.pone.0023629", "pui"=>"362461749", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "sgr"=>"80052293917"}, "id"=>"1c31f5df-6490-3f99-a48c-0656af7b8e73", "abstract"=>"BACKGROUND: BAFF, in addition to promoting B cell survival and differentiation, may affect T cells. The objective of this study was to determine the effect of BAFF on Th17 cell generation and its ramifications for the Th17 cell-driven disease, EAE.\\n\\nMETHODOLOGY/PRINCIPAL FINDINGS: Th17 cells were increased in BAFF-Tg B6 (B6.BTg) mice and decreased in B6.Baff(-/-) mice. Th17 cells in B6.Baff(-/-) mice bearing a BAFF Tg (B6.Baff(-/-).BTg mice) were identical to those in B6.BTg mice, indicating that membrane BAFF is dispensable for Th17 cell generation as long as soluble BAFF is plentiful. In T + non-T cell criss-cross co-cultures, Th17 cell generation was greatest in cultures containing B6.BTg T cells and lowest in cultures containing B6.Baff(-/-) T cells, regardless of the source of non-T cells. In cultures containing only T cells, Th17 cell generation followed an identical pattern. CD4(+) cell expression of CD126 (IL-6R α chain) was increased in B6.BTg mice and decreased in B6.Baff(-/-) mice, and activation of STAT3 following stimulation with IL-6 + TGF-β was also greatest in B6.BTg cells and lowest in B6.Baff(-/-) cells. EAE was clinically and pathologically most severe in B6.BTg mice and least severe in B6.Baff(-/-) mice and correlated with MOG(35-55) peptide-induced Th17 cell responses.\\n\\nCONCLUSIONS/SIGNIFICANCE: Collectively, these findings document a contribution of BAFF to pathogenic Th17 cell responses and suggest that BAFF antagonism may be efficacious in Th17 cell-driven diseases.", "link"=>"http://www.mendeley.com/research/baff-promotes-th17-cells-aggravates-experimental-autoimmune-encephalomyelitis", "reader_count"=>26, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>4, "Researcher"=>5, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>5, "Student > Postgraduate"=>2, "Student > Master"=>4, "Other"=>1, "Lecturer"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>4, "Researcher"=>5, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>5, "Student > Postgraduate"=>2, "Student > Master"=>4, "Other"=>1, "Lecturer"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Biochemistry, Genetics and Molecular Biology"=>2, "Nursing and Health Professions"=>1, "Agricultural and Biological Sciences"=>9, "Medicine and Dentistry"=>9, "Psychology"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>9}, "Psychology"=>{"Psychology"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>9}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Unspecified"=>{"Unspecified"=>3}}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/741538"], "description"=>"<p>Panel A: LN cells were double-stained for CD4 and CD126 from the indicated mice. The dot plots reflect representative mice, with the values outside the parentheses indicating the percentages of CD126<sup>+</sup> cells within the CD4<sup>+</sup> population and the values inside the parentheses indicating the mean fluorescence intensity of the CD126<sup>+</sup> cell population. Panel B: Results (mean ± SEM) are presented for the 3 mice in each cohort. Panels C–D: Naive CD4<sup>+</sup> cells from the indicated mice were stimulated with IL-6 (10 ng/ml) + TGF-β (2 ng/ml) for the indicated periods of time (minutes) and were subjected to Western blot analysis for total Stat3, phosphorylated Stat3 (p-Stat3), and GADPH (panels C–D) and phosphorylated Smad3 (p-Smad3) and GADPH (panels E–F). The levels of p-Stat3 and p-Smad3 were normalized to GAPDH, with the ratios of p-Stat3 or p-Smad3 to GADPH at 30 minutes being arbitrarily assigned a value of 1. The results shown in panels C and E are representative of the 7 independent experiments, and the results shown in panels D and F are the mean ± SEM of these 7 experiments. *, p≤0.05; **, p≤0.01; ***, p≤0.001 in comparison to WT values.</p>", "links"=>[], "tags"=>["cd126", "il-6-triggered", "signaling", "cells", "b6"], "article_id"=>411893, "categories"=>["Ecology", "Immunology"], "users"=>["Xiaohui Zhou", "Zanxian Xia", "Qin Lan", "Julie Wang", "Wenru Su", "Yuan-Ping Han", "Huimin Fan", "Zhongmin Liu", "William Stohl", "Song Guo Zheng"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0023629.g004", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Differential_CD126_expression_and_IL_6_triggered_signaling_in_CD4_cells_from_B6_WT_B6_Baff_8722_8722_and_B6_BTg_mice_/411893", "title"=>"Differential CD126 expression and IL-6-triggered signaling in CD4<sup>+</sup> cells from B6 WT, B6.<i>Baff<sup>−/−</sup></i>, and B6.BTg mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 15:19:10"}
  • {"files"=>["https://ndownloader.figshare.com/files/741232"], "description"=>"<p>T cells from spleen, blood, or LN of the indicated mice were cultured for 5 hr with PMA + ionomycin. Brefeldin A was added for the final 4 hr of culture to block secretion of cytokines and permit their accumulation intracellularly. Harvested cells were stained for surface CD4 and intracellular IL-17 (panel A), intracellular RORγt (panel B), or surface CCR-6 (panel C). *, p≤0.05; **, p≤0.01; ***, p≤0.001 in comparison to WT values.</p>", "links"=>[], "tags"=>["th17", "cells"], "article_id"=>411598, "categories"=>["Ecology", "Immunology"], "users"=>["Xiaohui Zhou", "Zanxian Xia", "Qin Lan", "Julie Wang", "Wenru Su", "Yuan-Ping Han", "Huimin Fan", "Zhongmin Liu", "William Stohl", "Song Guo Zheng"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0023629.g002", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Promotion_of_Th17_cells_by_BAFF_/411598", "title"=>"Promotion of Th17 cells by BAFF.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 15:17:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/741020"], "description"=>"<p>Panel A: Spleen (top) or LN (bottom) cells from representative B6 WT (WT), B6.<i>Baff<sup>−/−</sup></i> (KO), and B6.BTg (Tg) mice were stained for surface CD3 and surface CD19 expression. The values adjacent to the boxes in each tracing indicate the percentages of CD3<sup>+</sup> or CD19<sup>+</sup> cells in that sample. Panel B: Results (mean ± SEM) are presented for total spleen CD3<sup>+</sup>, CD4<sup>+</sup>, CD8<sup>+</sup>, and CD19<sup>+</sup> cells for the 6 mice in each cohort. Panel C: Results (mean ± SEM) are presented for LN CD4<sup>+</sup>CD69<sup>+</sup>, CD4<sup>+</sup>CD44<sup>hi</sup>, and CD4<sup>+</sup>CD62L<sup>lo</sup> cells for the 6 mice in each cohort. *, p≤0.05; **, p≤0.01; ***, p≤0.001 in comparison to WT values.</p>", "links"=>[], "tags"=>["cells", "mice"], "article_id"=>411387, "categories"=>["Ecology", "Immunology"], "users"=>["Xiaohui Zhou", "Zanxian Xia", "Qin Lan", "Julie Wang", "Wenru Su", "Yuan-Ping Han", "Huimin Fan", "Zhongmin Liu", "William Stohl", "Song Guo Zheng"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0023629.g001", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Decrease_in_both_B_cells_and_T_cells_in_B6_Baff_8722_8722_mice_and_increase_in_both_B_cells_and_T_cells_in_B6_BTg_mice_/411387", "title"=>"Decrease in both B cells and T cells in B6.<i>Baff<sup>−/−</sup></i> mice and increase in both B cells and T cells in B6.BTg mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 15:16:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/741372"], "description"=>"<p>Panel A: Spleen naive CD4<sup>+</sup> cells from the indicated mice (n = 4 in each cohort) were cultured for 3 days with anti-CD3 + anti-CD28 mAb (1 µg/ml each) in the presence of irradiated syngeneic non-T cells, IL-6 (10 ng/ml), TGF-β (2 ng/ml), and anti-IL-4 + anti-IFNγ antibodies (10 µg/ml each) and in the presence or absence of exogenous BAFF (100 ng/ml). Harvested cells were stained for surface CD4 and intracellular IL-17. Significantly (p≤0.01) greater percentages of CD4<sup>+</sup>IL-17<sup>+</sup> cells were generated in B6 WT cultures with added BAFF vs no added BAFF; in B6.<i>Baff<sup>−/−</sup></i> cultures with added BAFF vs no added BAFF; and in B6.BTg cultures with no added BAFF vs WT cultures with no added BAFF. Significantly (p≤0.01) reduced percentages of CD4<sup>+</sup>IL-17<sup>+</sup> cells were generated in B6.<i>Baff<sup>−/−</sup></i> cultures with added BAFF vs B6 WT cultures with no added BAFF. Panel B: Spleen naive CD4<sup>+</sup> cells from the indicated mice were co-cultured for 3 days with irradiated non-T cells from the indicated mice for 3 days as in panel A without exogenous BAFF. Harvested cells were stained for surface CD4 and intracellular IL-17. Panel C: Spleen naive CD4<sup>+</sup> cells from the indicated mice (n = 2 in each cohort) were cultured for 3 days as in panel A, except that no irradiated non-T cells were added to the cultures, and plate-bound anti-CD3 mAb (2 µg/ml) was used in place of soluble anti-CD3 mAb. *, p≤0.05; **, p≤0.01; ***, p≤0.001 in comparison to WT values.</p>", "links"=>[], "tags"=>["baff", "cells", "th17"], "article_id"=>411738, "categories"=>["Ecology", "Immunology"], "users"=>["Xiaohui Zhou", "Zanxian Xia", "Qin Lan", "Julie Wang", "Wenru Su", "Yuan-Ping Han", "Huimin Fan", "Zhongmin Liu", "William Stohl", "Song Guo Zheng"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0023629.g003", "stats"=>{"downloads"=>1, "page_views"=>19, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Direct_effect_of_BAFF_on_T_cells_in_generation_of_Th17_cells_/411738", "title"=>"Direct effect of BAFF on T cells in generation of Th17 cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 15:18:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/741678"], "description"=>"<p>Panel A: The indicated mice were immunized with MOG<sub>35–55</sub> in CFA and evaluated for clinical EAE. Results (mean ± SEM) are the aggregate of 3 independent experiments (each containing ≥3 mice per cohort). *, p<0.05; **, p<0.01; ***, p<0.001 in comparison to WT mice at the indicated time points. Panel B: T cells from the draining LN of the indicated mice were stimulated with PMA + ionomycin in the presence of brefeldin A as in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0023629#pone-0023629-g002\" target=\"_blank\">Figure 2</a> and stained for surface CD4 or CD8 and intracellular IL-17 or IFNγ. The values in the upper left quadrants in each tracing indicate the percentages of IL-17<sup>+</sup> cells (within the CD4<sup>+</sup> population) in that sample, and the values in the lower right quadrants indicate the percentages of IFNγ<sup>+</sup> cells (within the CD4<sup>+</sup> population). Results from a representative mouse from each cohort are shown. Panel C: Results are presented for CD4<sup>+</sup>IL-17<sup>+</sup> cells for the 3 mice in each cohort. Panel D: Draining LN cells from the MOG<sub>35–55</sub> peptide-immunized mice either were (+) or were not (−) cultured with MOG<sub>35–55</sub> peptide for 3 days. Percentages of CD4<sup>+</sup>IL-17<sup>+</sup> cells were determined. Results are presented for the 6 mice in each cohort (left) or a representative mouse from each cohort (right). ***, p<0.001. Panel E: Supernatants from the cultures in panel D were assayed for IL-17A. Results are presented as mean ± SEM. Panel F: The indicated mice were sacrificed on day 25 post-immunization, and sections of their brains and spinal cords were stained with H&E and immunostained for IL-17. Results are representative of the 6 mice in each cohort. Original magnification is 400×.</p>", "links"=>[], "tags"=>["severity", "eae", "mice", "th17"], "article_id"=>412037, "categories"=>["Ecology", "Immunology"], "users"=>["Xiaohui Zhou", "Zanxian Xia", "Qin Lan", "Julie Wang", "Wenru Su", "Yuan-Ping Han", "Huimin Fan", "Zhongmin Liu", "William Stohl", "Song Guo Zheng"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0023629.g005", "stats"=>{"downloads"=>2, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Differential_severity_of_EAE_in_B6_Baff_8722_8722_and_B6_BTg_mice_and_its_association_with_a_Th17_profile_/412037", "title"=>"Differential severity of EAE in B6.<i>Baff<sup>−/−</sup></i> and B6.BTg mice and its association with a Th17 profile.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 15:19:55"}

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