Soluble IL-2Rα (sCD25) Exacerbates Autoimmunity and Enhances the Development of Th17 Responses in Mice
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{"title"=>"Soluble IL-2Rα (sCD25) Exacerbates Autoimmunity and Enhances the Development of Th17 Responses in Mice", "type"=>"journal", "authors"=>[{"first_name"=>"Shane E.", "last_name"=>"Russell", "scopus_author_id"=>"56217065800"}, {"first_name"=>"Anne C.", "last_name"=>"Moore", "scopus_author_id"=>"37038094300"}, {"first_name"=>"Padraic G.", "last_name"=>"Fallon", "scopus_author_id"=>"7102455344"}, {"first_name"=>"Patrick T.", "last_name"=>"Walsh", "scopus_author_id"=>"7401934480"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"23077668", "issn"=>"19326203", "sgr"=>"84867515505", "pui"=>"365864539", "scopus"=>"2-s2.0-84867515505", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "doi"=>"10.1371/journal.pone.0047748"}, "id"=>"629c09d3-e1e5-3974-8e56-4cff452312cc", "abstract"=>"A strong association exists between mutations at the IL2 receptor alpha chain (CD25) gene locus and susceptibility to a number of T cell driven autoimmune diseases. Interestingly, the presence of certain CD25 susceptibility alleles has been correlated with significantly increased levels of the soluble form of CD25 (sCD25) in the serum of patients. However, the functional consequences, if any, of this observation are unknown. We have demonstrated that elevated levels of sCD25 in vivo resulted in exacerbated experimental autoimmune encephalomyelitis (EAE) and enhanced antigen-specific Th17 responses in the periphery. sCD25 exerted its effects early during the Th17 developmental programme in vitro, through inhibiting signalling downstream of the IL-2R. Although, sCD25 did not interact with the T cell surface, it specifically bound to secreted IL-2 demonstrating its ability to act as a decoy receptor for IL-2 in the T cell microenvironment. These data identify the ability of sCD25 to promote autoimmune disease pathogenesis and enhance Th17 responses through its ability to sequester local IL-2.", "link"=>"http://www.mendeley.com/research/soluble-il2r%CE%B1-scd25-exacerbates-autoimmunity-enhances-development-th17-responses-mice", "reader_count"=>29, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Librarian"=>1, "Researcher"=>7, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>6, "Student > Postgraduate"=>2, "Student > Master"=>4, "Other"=>3, "Student > Bachelor"=>2, "Lecturer > Senior Lecturer"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Librarian"=>1, "Researcher"=>7, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>6, "Student > Postgraduate"=>2, "Student > Master"=>4, "Other"=>3, "Student > Bachelor"=>2, "Lecturer > Senior Lecturer"=>1}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>5, "Agricultural and Biological Sciences"=>11, "Medicine and Dentistry"=>7, "Psychology"=>1, "Computer Science"=>2, "Immunology and Microbiology"=>3}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>7}, "Psychology"=>{"Psychology"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>3}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>11}, "Computer Science"=>{"Computer Science"=>2}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>5}}, "reader_count_by_country"=>{"United States"=>1, "Italy"=>2}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/559120"], "description"=>"<p>Purified naive CD4+ T cells from IL-17AeGFP reporter mice activated under Th17 inducing conditions in the presence of sCD25 (20 µg/ml) or anti-IL-2 (10 µg/ml) for 48 hrs and examined for levels of (<b>A</b>) IL-17A and (<b>B</b>) RORγT expression by FACS. All data are representative of at least 3 independent experiments.</p>", "links"=>[], "tags"=>["acts", "th17"], "article_id"=>229617, "categories"=>["Genetics", "Immunology"], "users"=>["Shane E. Russell", "Anne C. Moore", "Padraic G. Fallon", "Patrick T. Walsh"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0047748.g004", "stats"=>{"downloads"=>1, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_sCD25_acts_early_during_Th17_development_/229617", "title"=>"sCD25 acts early during Th17 development.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 21:45:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/559206"], "description"=>"<p>(<b>A–D</b>) Purified naive CD4+ T cells activated for 24 hrs under Th17 inducing conditions in the presence or absence of sCD25 and examined for levels of (<b>A</b>) p-Stat5 pY694, (<b>B</b>) intracellular IL-2 expression (<b>C</b>) surface binding of sCD25-His and (<b>D</b>) surface expression of endogenous CD25 by FACS analysis. (<b>E</b>) Levels of secreted IL-2 detected by ELISA 24 hours after Th17 activation in the presence of decreasing doses of sCD25 (20,10,5,1 µg/ml). (<b>F</b>) Levels of IL-2/sCD25 complex in the supernatants of Th17 cells activated for 24 hours in the presence or absence of sCD25 (20 µg/ml). Data shown as mean +/− standard deviation from triplicate experiments. All data are representative of at least 3 independent experiments. Statistical Significance determined by unpaired student's t-test, ***p≤0.001.</p>", "links"=>[], "tags"=>["inhibits", "il-2r", "signalling", "sequestering", "secreted"], "article_id"=>229703, "categories"=>["Genetics", "Immunology"], "users"=>["Shane E. Russell", "Anne C. Moore", "Padraic G. Fallon", "Patrick T. Walsh"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0047748.g005", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_sCD25_inhibits_IL_2R_signalling_by_sequestering_secreted_IL_2_/229703", "title"=>"sCD25 inhibits IL-2R signalling by sequestering secreted IL-2.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 21:46:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/558943"], "description"=>"<p>(<b>A</b>) Levels of IL-17A and IFNγ secreted by draining lymph node cells of mice immunized and treated as above (3 per group), isolated after 9 days, and restimulated <i>ex vivo</i> with MOG<sub>33−55</sub> (10 µg/ml) for 72 hours. (<b>B</b>) Percentage of CD4+ IL-17A-eGFP+ve cells after treatment as above and <i>ex vivo</i> restimulation for 72 hours. (<b>C</b>) Percentage and (<b>D</b>) relative number ratios of CD4+FoxP3+:CD4+FoxP3- T cells in the draining lymph nodes of both sCD25 and control treated immunized mice. 3 mice per group were analysed. Data in D & G is representative of mean +/− standard deviation. Statistical Significance determined by unpaired student's t-test, * p≤0.05, **p≤0.01.</p>", "links"=>[], "tags"=>["enhances", "peripheral", "antigen", "th17"], "article_id"=>229436, "categories"=>["Genetics", "Immunology"], "users"=>["Shane E. Russell", "Anne C. Moore", "Padraic G. Fallon", "Patrick T. Walsh"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0047748.g002", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_sCD25_enhances_peripheral_antigen_specific_Th17_responses_/229436", "title"=>"sCD25 enhances peripheral antigen specific Th17 responses.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 21:44:33"}
  • {"files"=>["https://ndownloader.figshare.com/files/558839"], "description"=>"<p>(<b>A</b>) MOG<sub>33−55</sub> immunized C57BL/6 mice developed clinical symptoms of EAE from day 12 after immunization with a peak of disease severity observed from day 19. Subcutaneous administration of recombinant sCD25 (25 µg/mouse) immediately prior to immunization and every 12 hours thereafter for 72 hrs resulted in a significant exacerbation in severity of symptoms during disease onset and induction. 6–7 mice used per group. (<b>B</b>) Mononuclear cells harvested from spinal cords of control (PBS) and sCD25 treated IL-17A-eGFP reporter mice (3 per group) on day 15 after immunization and analysed for expression of IL-17 and IFN-γ by CD4+ cells. (<b>C</b>) Cell numbers of CD4+IL-17+ and CD4+ IFNγ+ cells in spinal cords of IL-17A-eGFP reporter mice at day 15. Data representative of mean +/− std dev of 3 mice per group and 2 independent experiments.</p>", "links"=>[], "tags"=>["scd25", "exacerbates"], "article_id"=>229333, "categories"=>["Genetics", "Immunology"], "users"=>["Shane E. Russell", "Anne C. Moore", "Padraic G. Fallon", "Patrick T. Walsh"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0047748.g001", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Exogenous_sCD25_exacerbates_autoimmunity_/229333", "title"=>"Exogenous sCD25 exacerbates autoimmunity.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 21:43:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/559045"], "description"=>"<p>(<b>A&B</b>) Purified naive CD4+ T cells were activated under either Th17 or Th1 inducing conditions (as described in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0047748#s2\" target=\"_blank\">methods</a>) in the presence of a range of concentrations of sCD25 (20, 10, 5 or 1 µg/ml) or anti-IL-2 (10 µg/ml). Levels of IL-17A or IFNγ expression were determined after 96 hrs by (<b>A</b>) FACS and (<b>B</b>) ELISA. (<b>C</b>) Purified naive CD4+ T cells were activated under Treg inducing conditions, as described in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0047748#s2\" target=\"_blank\">methods</a>, in the presence or absence of sCD25 (20µg/ml) and FoxP3 expression determined by FACS. (<b>D</b>) Naive CD4+ T cells were stained with CFSE (2.5 µM) prior to activation under Th17 conditions in presence or absence of sCD25 (20 µg/ml). After 96 hours, levels of intracellular IL-17A expression and CFSE dilution or 7AAD incorporation were determined by FACS. (<b>E</b>) Purified naive CD4+ T cells were activated under Th0, Th17 and Th17& sCD25 (20 µg/ml) conditions for 72 hours and levels of P-Stat3 (pY705) determined by FACS. All data are representative of 3 independent experiments. Statistical Significance determined by unpaired student's t-test, ∗ p≤0.05, **p≤0.01, ***p≤0.001.</p>", "links"=>[], "tags"=>["enhances", "th17", "responses"], "article_id"=>229541, "categories"=>["Genetics", "Immunology"], "users"=>["Shane E. Russell", "Anne C. Moore", "Padraic G. Fallon", "Patrick T. Walsh"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0047748.g003", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_sCD25_enhances_Th17_cell_responses_in_vitro_/229541", "title"=>"sCD25 enhances Th17 cell responses <i>in vitro</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 21:45:11"}

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Relative Metric

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