A novel role for lipoxin A4 in driving a lymph node–eye axis that controls autoimmunity to the neuroretina
The eicosanoid lipoxin A4 (LXA4) has emerging roles in lymphocyte-driven diseases. We identified reduced LXA4 levels in posterior segment uveitis patients and investigated the role of LXA4 in the pathogenesis of experimental autoimmune uveitis (EAU). Immunization for EAU with a retinal self-antigen...
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eLife Sciences Publications Ltd
2020-03-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/51102 |
| _version_ | 1818026822678347776 |
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| author | Jessica Wei Mary J Mattapallil Reiko Horai Yingyos Jittayasothorn Arnav P Modi H Nida Sen Karsten Gronert Rachel R Caspi |
| author_facet | Jessica Wei Mary J Mattapallil Reiko Horai Yingyos Jittayasothorn Arnav P Modi H Nida Sen Karsten Gronert Rachel R Caspi |
| author_sort | Jessica Wei |
| collection | DOAJ |
| description | The eicosanoid lipoxin A4 (LXA4) has emerging roles in lymphocyte-driven diseases. We identified reduced LXA4 levels in posterior segment uveitis patients and investigated the role of LXA4 in the pathogenesis of experimental autoimmune uveitis (EAU). Immunization for EAU with a retinal self-antigen caused selective downregulation of LXA4 in lymph nodes draining the site of immunization, while at the same time amplifying LXA4 in the inflamed target tissue. T cell effector function, migration and glycolytic responses were amplified in LXA4-deficient mice, which correlated with more severe pathology, whereas LXA4 treatment attenuated disease. In vivo deletion or supplementation of LXA4 identified modulation of CC-chemokine receptor 7 (CCR7) and sphingosine 1- phosphate receptor-1 (S1PR1) expression and glucose metabolism in CD4+ T cells as potential mechanisms for LXA4 regulation of T cell effector function and trafficking. Our results demonstrate the intrinsic lymph node LXA4 pathway as a significant checkpoint in the development and severity of adaptive immunity. |
| first_indexed | 2024-12-10T04:38:07Z |
| format | Article |
| id | doaj.art-1478210c54f44cb39b611f01a50ed664 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-12-10T04:38:07Z |
| publishDate | 2020-03-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
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| spelling | doaj.art-1478210c54f44cb39b611f01a50ed6642022-12-22T02:01:57ZengeLife Sciences Publications LtdeLife2050-084X2020-03-01910.7554/eLife.51102A novel role for lipoxin A4 in driving a lymph node–eye axis that controls autoimmunity to the neuroretinaJessica Wei0https://orcid.org/0000-0002-7329-2812Mary J Mattapallil1Reiko Horai2Yingyos Jittayasothorn3Arnav P Modi4H Nida Sen5Karsten Gronert6https://orcid.org/0000-0002-5329-7907Rachel R Caspi7Vision Science Program, University of California, Berkeley, Berkeley, United States; Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, United StatesLaboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, United StatesLaboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, United StatesLaboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, United StatesSchool of Optometry, University of California, Berkeley, Berkeley, United StatesLaboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, United StatesVision Science Program, University of California, Berkeley, Berkeley, United States; School of Optometry, University of California, Berkeley, Berkeley, United States; Infectious Disease and Immunity Program, University of California, Berkeley, Berkeley, United StatesLaboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, United StatesThe eicosanoid lipoxin A4 (LXA4) has emerging roles in lymphocyte-driven diseases. We identified reduced LXA4 levels in posterior segment uveitis patients and investigated the role of LXA4 in the pathogenesis of experimental autoimmune uveitis (EAU). Immunization for EAU with a retinal self-antigen caused selective downregulation of LXA4 in lymph nodes draining the site of immunization, while at the same time amplifying LXA4 in the inflamed target tissue. T cell effector function, migration and glycolytic responses were amplified in LXA4-deficient mice, which correlated with more severe pathology, whereas LXA4 treatment attenuated disease. In vivo deletion or supplementation of LXA4 identified modulation of CC-chemokine receptor 7 (CCR7) and sphingosine 1- phosphate receptor-1 (S1PR1) expression and glucose metabolism in CD4+ T cells as potential mechanisms for LXA4 regulation of T cell effector function and trafficking. Our results demonstrate the intrinsic lymph node LXA4 pathway as a significant checkpoint in the development and severity of adaptive immunity.https://elifesciences.org/articles/51102effector t cells5-lipoxygenaseuveitistraffickingCcr7draining lymph node |
| spellingShingle | Jessica Wei Mary J Mattapallil Reiko Horai Yingyos Jittayasothorn Arnav P Modi H Nida Sen Karsten Gronert Rachel R Caspi A novel role for lipoxin A4 in driving a lymph node–eye axis that controls autoimmunity to the neuroretina eLife effector t cells 5-lipoxygenase uveitis trafficking Ccr7 draining lymph node |
| title | A novel role for lipoxin A4 in driving a lymph node–eye axis that controls autoimmunity to the neuroretina |
| title_full | A novel role for lipoxin A4 in driving a lymph node–eye axis that controls autoimmunity to the neuroretina |
| title_fullStr | A novel role for lipoxin A4 in driving a lymph node–eye axis that controls autoimmunity to the neuroretina |
| title_full_unstemmed | A novel role for lipoxin A4 in driving a lymph node–eye axis that controls autoimmunity to the neuroretina |
| title_short | A novel role for lipoxin A4 in driving a lymph node–eye axis that controls autoimmunity to the neuroretina |
| title_sort | novel role for lipoxin a4 in driving a lymph node eye axis that controls autoimmunity to the neuroretina |
| topic | effector t cells 5-lipoxygenase uveitis trafficking Ccr7 draining lymph node |
| url | https://elifesciences.org/articles/51102 |
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