Adenosine A2A Receptor Deletion Blocks the Beneficial Effects of Lactobacillus reuteri in Regulatory T-Deficient Scurfy Mice
The lack of a functional Foxp3 transcription factor and regulatory T (Treg) cells causes lethal, CD4+ T cell-driven autoimmune diseases in scurfy (SF) mice and humans. Recent studies have shown that adenosine A2A receptor activation limits inflammation and tissue damage, thereby playing an anti-infl...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2017.01680/full |
| _version_ | 1818853471507447808 |
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| author | Baokun He Thomas K. Hoang Dat Q. Tran Jon Marc Rhoads Yuying Liu |
| author_facet | Baokun He Thomas K. Hoang Dat Q. Tran Jon Marc Rhoads Yuying Liu |
| author_sort | Baokun He |
| collection | DOAJ |
| description | The lack of a functional Foxp3 transcription factor and regulatory T (Treg) cells causes lethal, CD4+ T cell-driven autoimmune diseases in scurfy (SF) mice and humans. Recent studies have shown that adenosine A2A receptor activation limits inflammation and tissue damage, thereby playing an anti-inflammatory role. However, the role of the adenosine A2A receptor in the development of disease in SF mice remains unclear. Using a genetic approach, we found that adenosine A2A receptor deletion in SF mice (SF⋅A2A-/-) does not affect early life events, the development of a lymphoproliferative disorder, or hyper-production of pro-inflammatory cytokines seen in the Treg-deficiency state. As shown previously, Lactobacillus reuteri DSM 17938 treatment prolonged survival and reduced multiorgan inflammation in SF mice. In marked contrast, A2A receptor deletion completely blocked these beneficial effects of L. reuteri in SF mice. Altogether, these results suggest that although absence of the adenosine A2A receptor does not affect the development of disease in SF mice, it plays a critical role in the immunomodulation by L. reuteri in Treg-deficiency disease. The adenosine A2A receptor and its activation may have a role in treating other Treg dysfunction-mediated autoimmune diseases. |
| first_indexed | 2024-12-19T07:37:21Z |
| format | Article |
| id | doaj.art-8b4589a4c0ac4dda8a429b15aada7335 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-19T07:37:21Z |
| publishDate | 2017-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-8b4589a4c0ac4dda8a429b15aada73352022-12-21T20:30:33ZengFrontiers Media S.A.Frontiers in Immunology1664-32242017-12-01810.3389/fimmu.2017.01680304990Adenosine A2A Receptor Deletion Blocks the Beneficial Effects of Lactobacillus reuteri in Regulatory T-Deficient Scurfy MiceBaokun He0Thomas K. Hoang1Dat Q. Tran2Jon Marc Rhoads3Yuying Liu4Division of Gastroenterology, Department of Pediatrics, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, United StatesDivision of Gastroenterology, Department of Pediatrics, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, United StatesDivision of Gastroenterology, Department of Pediatrics, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, United StatesDivision of Gastroenterology, Department of Pediatrics, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, United StatesDivision of Gastroenterology, Department of Pediatrics, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, United StatesThe lack of a functional Foxp3 transcription factor and regulatory T (Treg) cells causes lethal, CD4+ T cell-driven autoimmune diseases in scurfy (SF) mice and humans. Recent studies have shown that adenosine A2A receptor activation limits inflammation and tissue damage, thereby playing an anti-inflammatory role. However, the role of the adenosine A2A receptor in the development of disease in SF mice remains unclear. Using a genetic approach, we found that adenosine A2A receptor deletion in SF mice (SF⋅A2A-/-) does not affect early life events, the development of a lymphoproliferative disorder, or hyper-production of pro-inflammatory cytokines seen in the Treg-deficiency state. As shown previously, Lactobacillus reuteri DSM 17938 treatment prolonged survival and reduced multiorgan inflammation in SF mice. In marked contrast, A2A receptor deletion completely blocked these beneficial effects of L. reuteri in SF mice. Altogether, these results suggest that although absence of the adenosine A2A receptor does not affect the development of disease in SF mice, it plays a critical role in the immunomodulation by L. reuteri in Treg-deficiency disease. The adenosine A2A receptor and its activation may have a role in treating other Treg dysfunction-mediated autoimmune diseases.http://journal.frontiersin.org/article/10.3389/fimmu.2017.01680/fullregulatory T deficiencyautoimmunityadenosine A2A receptorLactobacillus reutericytokinesIPEX |
| spellingShingle | Baokun He Thomas K. Hoang Dat Q. Tran Jon Marc Rhoads Yuying Liu Adenosine A2A Receptor Deletion Blocks the Beneficial Effects of Lactobacillus reuteri in Regulatory T-Deficient Scurfy Mice Frontiers in Immunology regulatory T deficiency autoimmunity adenosine A2A receptor Lactobacillus reuteri cytokines IPEX |
| title | Adenosine A2A Receptor Deletion Blocks the Beneficial Effects of Lactobacillus reuteri in Regulatory T-Deficient Scurfy Mice |
| title_full | Adenosine A2A Receptor Deletion Blocks the Beneficial Effects of Lactobacillus reuteri in Regulatory T-Deficient Scurfy Mice |
| title_fullStr | Adenosine A2A Receptor Deletion Blocks the Beneficial Effects of Lactobacillus reuteri in Regulatory T-Deficient Scurfy Mice |
| title_full_unstemmed | Adenosine A2A Receptor Deletion Blocks the Beneficial Effects of Lactobacillus reuteri in Regulatory T-Deficient Scurfy Mice |
| title_short | Adenosine A2A Receptor Deletion Blocks the Beneficial Effects of Lactobacillus reuteri in Regulatory T-Deficient Scurfy Mice |
| title_sort | adenosine a2a receptor deletion blocks the beneficial effects of lactobacillus reuteri in regulatory t deficient scurfy mice |
| topic | regulatory T deficiency autoimmunity adenosine A2A receptor Lactobacillus reuteri cytokines IPEX |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2017.01680/full |
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