Secretion of autoimmune antibodies in the human subcutaneous adipose tissue.
The adipose tissue (AT) contributes to systemic and B cell intrinsic inflammation, reduced B cell responses and secretion of autoimmune antibodies. In this study we show that adipocytes in the human obese subcutaneous AT (SAT) secrete several pro-inflammatory cytokines and chemokines, which contribu...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2018-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5955545?pdf=render |
| _version_ | 1811321598728208384 |
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| author | Daniela Frasca Alain Diaz Maria Romero Seth Thaller Bonnie B Blomberg |
| author_facet | Daniela Frasca Alain Diaz Maria Romero Seth Thaller Bonnie B Blomberg |
| author_sort | Daniela Frasca |
| collection | DOAJ |
| description | The adipose tissue (AT) contributes to systemic and B cell intrinsic inflammation, reduced B cell responses and secretion of autoimmune antibodies. In this study we show that adipocytes in the human obese subcutaneous AT (SAT) secrete several pro-inflammatory cytokines and chemokines, which contribute to the establishment and maintenance of local and systemic inflammation, and consequent suboptimal immune responses in obese individuals, as we have previously shown. We also show that pro-inflammatory chemokines recruit immune cells expressing the corresponding receptors to the SAT, where they also contribute to local and systemic inflammation, secreting additional pro-inflammatory mediators. Moreover, we show that the SAT generates autoimmune antibodies. During the development of obesity, reduced oxygen and consequent hypoxia and cell death lead to further release of pro-inflammatory cytokines, "self" protein antigens, cell-free DNA and lipids. All these stimulate class switch and the production of autoimmune IgG antibodies which have been described to be pathogenic. In addition to hypoxia, we have measured cell cytotoxicity and DNA damage mechanisms, which may also contribute to the release of "self" antigens in the SAT. All these processes are significantly elevated in the SAT as compared to the blood. We definitively found that fat-specific IgG antibodies are secreted by B cells in the SAT and that B cells express mRNA for the transcription factor T-bet and the membrane marker CD11c, both involved in the production of autoimmune IgG antibodies. Finally, the SAT also expresses RNA for cytokines known to promote Germinal Center formation, isotype class switch, and plasma cell differentiation. Our results show novel mechanisms for the generation of autoimmune antibody responses in the human SAT and allow the identification of new pathways to possibly manipulate in order to reduce systemic inflammation and autoantibody production in obese individuals. |
| first_indexed | 2024-04-13T13:19:40Z |
| format | Article |
| id | doaj.art-4a3496d2ca114a628e295ddc025578dd |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T13:19:40Z |
| publishDate | 2018-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-4a3496d2ca114a628e295ddc025578dd2022-12-22T02:45:21ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01135e019747210.1371/journal.pone.0197472Secretion of autoimmune antibodies in the human subcutaneous adipose tissue.Daniela FrascaAlain DiazMaria RomeroSeth ThallerBonnie B BlombergThe adipose tissue (AT) contributes to systemic and B cell intrinsic inflammation, reduced B cell responses and secretion of autoimmune antibodies. In this study we show that adipocytes in the human obese subcutaneous AT (SAT) secrete several pro-inflammatory cytokines and chemokines, which contribute to the establishment and maintenance of local and systemic inflammation, and consequent suboptimal immune responses in obese individuals, as we have previously shown. We also show that pro-inflammatory chemokines recruit immune cells expressing the corresponding receptors to the SAT, where they also contribute to local and systemic inflammation, secreting additional pro-inflammatory mediators. Moreover, we show that the SAT generates autoimmune antibodies. During the development of obesity, reduced oxygen and consequent hypoxia and cell death lead to further release of pro-inflammatory cytokines, "self" protein antigens, cell-free DNA and lipids. All these stimulate class switch and the production of autoimmune IgG antibodies which have been described to be pathogenic. In addition to hypoxia, we have measured cell cytotoxicity and DNA damage mechanisms, which may also contribute to the release of "self" antigens in the SAT. All these processes are significantly elevated in the SAT as compared to the blood. We definitively found that fat-specific IgG antibodies are secreted by B cells in the SAT and that B cells express mRNA for the transcription factor T-bet and the membrane marker CD11c, both involved in the production of autoimmune IgG antibodies. Finally, the SAT also expresses RNA for cytokines known to promote Germinal Center formation, isotype class switch, and plasma cell differentiation. Our results show novel mechanisms for the generation of autoimmune antibody responses in the human SAT and allow the identification of new pathways to possibly manipulate in order to reduce systemic inflammation and autoantibody production in obese individuals.http://europepmc.org/articles/PMC5955545?pdf=render |
| spellingShingle | Daniela Frasca Alain Diaz Maria Romero Seth Thaller Bonnie B Blomberg Secretion of autoimmune antibodies in the human subcutaneous adipose tissue. PLoS ONE |
| title | Secretion of autoimmune antibodies in the human subcutaneous adipose tissue. |
| title_full | Secretion of autoimmune antibodies in the human subcutaneous adipose tissue. |
| title_fullStr | Secretion of autoimmune antibodies in the human subcutaneous adipose tissue. |
| title_full_unstemmed | Secretion of autoimmune antibodies in the human subcutaneous adipose tissue. |
| title_short | Secretion of autoimmune antibodies in the human subcutaneous adipose tissue. |
| title_sort | secretion of autoimmune antibodies in the human subcutaneous adipose tissue |
| url | http://europepmc.org/articles/PMC5955545?pdf=render |
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