Peak inflammation in atherosclerosis, primary biliary cirrhosis and autoimmune arthritis is counter-intuitively associated with regulatory T cell enrichment
© 2015 The Authors. Regulatory T cells (Treg) influence the development of autoimmunity and their use is increasingly proposed for clinical applications. The well-characterized suppressive potential of Treg frequently leads to the assumption that Treg presence in prevailing numbers is indicative of...
| Main Authors: | , , , , , , , , |
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| Format: | Journal Article |
| Published: |
Urban and Fischer Verlag
2015
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| Online Access: | http://hdl.handle.net/20.500.11937/56389 |
| _version_ | 1848759862986539008 |
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| author | Garetto, S. Trovato, A. Lleo, A. Sala, F. Martini, E. Betz, A. Norata, Giuseppe Invernizzi, P. Kallikourdis, M. |
| author_facet | Garetto, S. Trovato, A. Lleo, A. Sala, F. Martini, E. Betz, A. Norata, Giuseppe Invernizzi, P. Kallikourdis, M. |
| author_sort | Garetto, S. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | © 2015 The Authors. Regulatory T cells (Treg) influence the development of autoimmunity and their use is increasingly proposed for clinical applications. The well-characterized suppressive potential of Treg frequently leads to the assumption that Treg presence in prevailing numbers is indicative of immunosuppression. We hypothesized that this assumption may be false. We examined models of three different diseases caused by organ-specific autoimmune responses: primary biliary cirrhosis, atherosclerosis and rheumatoid arthritis (RA). We examined indicators of relative abundance of Treg compared to pro-inflammatory T cells, during peak inflammation. In all cases, the results were compatible with a relative enrichment of Treg at the site of inflammation or its most proximal draining lymph node. Conversely, in healthy mice or mice successfully protected from disease via a Treg-mediated mechanism, the data did not suggest that any Treg accumulation was occurring. This counter-intuitive finding may appear to be at odds with the immunosuppressive nature of Treg. Yet extensive previous studies in RA show that an accumulation of Treg occurs at peak inflammation, albeit without resulting in suppression, as the Treg suppressive function is overcome by the cytokine-rich environment. We suggest that this is a ubiquitous feature of autoimmune inflammation. Treg abundance in patient samples is increasingly used as an indicator of a state of immunosuppression. We conclude that this strategy should be revisited as it may potentially be a source of misinterpretation. |
| first_indexed | 2025-11-14T10:06:38Z |
| format | Journal Article |
| id | curtin-20.500.11937-56389 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T10:06:38Z |
| publishDate | 2015 |
| publisher | Urban and Fischer Verlag |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-563892017-09-13T16:10:18Z Peak inflammation in atherosclerosis, primary biliary cirrhosis and autoimmune arthritis is counter-intuitively associated with regulatory T cell enrichment Garetto, S. Trovato, A. Lleo, A. Sala, F. Martini, E. Betz, A. Norata, Giuseppe Invernizzi, P. Kallikourdis, M. © 2015 The Authors. Regulatory T cells (Treg) influence the development of autoimmunity and their use is increasingly proposed for clinical applications. The well-characterized suppressive potential of Treg frequently leads to the assumption that Treg presence in prevailing numbers is indicative of immunosuppression. We hypothesized that this assumption may be false. We examined models of three different diseases caused by organ-specific autoimmune responses: primary biliary cirrhosis, atherosclerosis and rheumatoid arthritis (RA). We examined indicators of relative abundance of Treg compared to pro-inflammatory T cells, during peak inflammation. In all cases, the results were compatible with a relative enrichment of Treg at the site of inflammation or its most proximal draining lymph node. Conversely, in healthy mice or mice successfully protected from disease via a Treg-mediated mechanism, the data did not suggest that any Treg accumulation was occurring. This counter-intuitive finding may appear to be at odds with the immunosuppressive nature of Treg. Yet extensive previous studies in RA show that an accumulation of Treg occurs at peak inflammation, albeit without resulting in suppression, as the Treg suppressive function is overcome by the cytokine-rich environment. We suggest that this is a ubiquitous feature of autoimmune inflammation. Treg abundance in patient samples is increasingly used as an indicator of a state of immunosuppression. We conclude that this strategy should be revisited as it may potentially be a source of misinterpretation. 2015 Journal Article http://hdl.handle.net/20.500.11937/56389 10.1016/j.imbio.2015.02.006 Urban and Fischer Verlag unknown |
| spellingShingle | Garetto, S. Trovato, A. Lleo, A. Sala, F. Martini, E. Betz, A. Norata, Giuseppe Invernizzi, P. Kallikourdis, M. Peak inflammation in atherosclerosis, primary biliary cirrhosis and autoimmune arthritis is counter-intuitively associated with regulatory T cell enrichment |
| title | Peak inflammation in atherosclerosis, primary biliary cirrhosis and autoimmune arthritis is counter-intuitively associated with regulatory T cell enrichment |
| title_full | Peak inflammation in atherosclerosis, primary biliary cirrhosis and autoimmune arthritis is counter-intuitively associated with regulatory T cell enrichment |
| title_fullStr | Peak inflammation in atherosclerosis, primary biliary cirrhosis and autoimmune arthritis is counter-intuitively associated with regulatory T cell enrichment |
| title_full_unstemmed | Peak inflammation in atherosclerosis, primary biliary cirrhosis and autoimmune arthritis is counter-intuitively associated with regulatory T cell enrichment |
| title_short | Peak inflammation in atherosclerosis, primary biliary cirrhosis and autoimmune arthritis is counter-intuitively associated with regulatory T cell enrichment |
| title_sort | peak inflammation in atherosclerosis, primary biliary cirrhosis and autoimmune arthritis is counter-intuitively associated with regulatory t cell enrichment |
| url | http://hdl.handle.net/20.500.11937/56389 |