T cell and dendritic cell abnormalities synergize to expand pro-inflammatory T cell subsets leading to fatal autoimmunity in B6.NZBc1 lupus-prone mice.
We have previously shown that B6 congenic mice with a New Zealand Black chromosome 1 (c1) 96-100 cM interval produce anti-nuclear Abs and that at least two additional genetic loci are required to convert this subclinical disease to fatal glomerulonephritis in mice with a c1 70-100 cM interval (c1(70...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3779178?pdf=render |
| _version_ | 1828775580361818112 |
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| author | Nafiseh Talaei Yui-Ho Cheung Carolina Landolt-Marticorena Babak Noamani Timothy Li Joan E Wither |
| author_facet | Nafiseh Talaei Yui-Ho Cheung Carolina Landolt-Marticorena Babak Noamani Timothy Li Joan E Wither |
| author_sort | Nafiseh Talaei |
| collection | DOAJ |
| description | We have previously shown that B6 congenic mice with a New Zealand Black chromosome 1 (c1) 96-100 cM interval produce anti-nuclear Abs and that at least two additional genetic loci are required to convert this subclinical disease to fatal glomerulonephritis in mice with a c1 70-100 cM interval (c1(70-100)). Here we show that the number of T follicular helper and IL-21-, IFN-γ-, and IL-17-secreting CD4(+) T cells parallels disease severity and the number of susceptibility loci in these mice. Immunization of pre-autoimmune mice with OVA recapitulated these differences. Differentiation of naïve T cells in-vitro under polarizing conditions and in-vivo following adoptive transfer of OVA-specific TCR transgenic cells into c1(70-100) or B6 recipient mice, revealed T cell functional defects leading to increased differentiation of IFN-γ- and IL-17-producing cells in the 96-100 cM and 88-96 cM intervals, respectively. However, in-vivo enhanced differentiation of pro-inflammatory T cell subsets was predominantly restricted to c1(70-100) recipient mice, which demonstrated altered dendritic cell function, with increased production of IL-6 and IL-12. The data provide support for the role of pro-inflammatory T cells in the conversion of subclinical disease to fatal autoimmunity and highlight the importance of synergistic interactions between individual susceptibility loci in this process. |
| first_indexed | 2024-12-11T15:42:47Z |
| format | Article |
| id | doaj.art-dd8dc6b818a941f28c9ee44c2778d124 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T15:42:47Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-dd8dc6b818a941f28c9ee44c2778d1242022-12-22T00:59:47ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0189e7516610.1371/journal.pone.0075166T cell and dendritic cell abnormalities synergize to expand pro-inflammatory T cell subsets leading to fatal autoimmunity in B6.NZBc1 lupus-prone mice.Nafiseh TalaeiYui-Ho CheungCarolina Landolt-MarticorenaBabak NoamaniTimothy LiJoan E WitherWe have previously shown that B6 congenic mice with a New Zealand Black chromosome 1 (c1) 96-100 cM interval produce anti-nuclear Abs and that at least two additional genetic loci are required to convert this subclinical disease to fatal glomerulonephritis in mice with a c1 70-100 cM interval (c1(70-100)). Here we show that the number of T follicular helper and IL-21-, IFN-γ-, and IL-17-secreting CD4(+) T cells parallels disease severity and the number of susceptibility loci in these mice. Immunization of pre-autoimmune mice with OVA recapitulated these differences. Differentiation of naïve T cells in-vitro under polarizing conditions and in-vivo following adoptive transfer of OVA-specific TCR transgenic cells into c1(70-100) or B6 recipient mice, revealed T cell functional defects leading to increased differentiation of IFN-γ- and IL-17-producing cells in the 96-100 cM and 88-96 cM intervals, respectively. However, in-vivo enhanced differentiation of pro-inflammatory T cell subsets was predominantly restricted to c1(70-100) recipient mice, which demonstrated altered dendritic cell function, with increased production of IL-6 and IL-12. The data provide support for the role of pro-inflammatory T cells in the conversion of subclinical disease to fatal autoimmunity and highlight the importance of synergistic interactions between individual susceptibility loci in this process.http://europepmc.org/articles/PMC3779178?pdf=render |
| spellingShingle | Nafiseh Talaei Yui-Ho Cheung Carolina Landolt-Marticorena Babak Noamani Timothy Li Joan E Wither T cell and dendritic cell abnormalities synergize to expand pro-inflammatory T cell subsets leading to fatal autoimmunity in B6.NZBc1 lupus-prone mice. PLoS ONE |
| title | T cell and dendritic cell abnormalities synergize to expand pro-inflammatory T cell subsets leading to fatal autoimmunity in B6.NZBc1 lupus-prone mice. |
| title_full | T cell and dendritic cell abnormalities synergize to expand pro-inflammatory T cell subsets leading to fatal autoimmunity in B6.NZBc1 lupus-prone mice. |
| title_fullStr | T cell and dendritic cell abnormalities synergize to expand pro-inflammatory T cell subsets leading to fatal autoimmunity in B6.NZBc1 lupus-prone mice. |
| title_full_unstemmed | T cell and dendritic cell abnormalities synergize to expand pro-inflammatory T cell subsets leading to fatal autoimmunity in B6.NZBc1 lupus-prone mice. |
| title_short | T cell and dendritic cell abnormalities synergize to expand pro-inflammatory T cell subsets leading to fatal autoimmunity in B6.NZBc1 lupus-prone mice. |
| title_sort | t cell and dendritic cell abnormalities synergize to expand pro inflammatory t cell subsets leading to fatal autoimmunity in b6 nzbc1 lupus prone mice |
| url | http://europepmc.org/articles/PMC3779178?pdf=render |
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