Th17 cytokines differentiate obesity from obesity-associated type 2 diabetes and promote TNFα production
Objective: T cell inflammation plays pivotal roles in obesity-associated type 2 diabetes (T2DM). The identification of dominant sources of T cell inflammation in humans remains a significant gap in understanding disease pathogenesis. It was hypothesized that cytokine profiles from circulating T cell...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Nature Publishing Group
2017
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| Online Access: | http://hdl.handle.net/1721.1/106829 |
| _version_ | 1826208616024113152 |
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| author | Ip, Blanche Belkina, Anna C. DeFuria, Jason Jagannathan-Bogdan, Madhumita Zhu, Min Kuchibhatla, Ramya McDonnell, Marie E. Xiao, Qiang Kepler, Thomas B. Apovian, Caroline M. Nikolajczyk, Barbara S. Cilfone, Nicholas A. Lauffenburger, Douglas A |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Ip, Blanche Belkina, Anna C. DeFuria, Jason Jagannathan-Bogdan, Madhumita Zhu, Min Kuchibhatla, Ramya McDonnell, Marie E. Xiao, Qiang Kepler, Thomas B. Apovian, Caroline M. Nikolajczyk, Barbara S. Cilfone, Nicholas A. Lauffenburger, Douglas A |
| author_sort | Ip, Blanche |
| collection | MIT |
| description | Objective: T cell inflammation plays pivotal roles in obesity-associated type 2 diabetes (T2DM). The identification of dominant sources of T cell inflammation in humans remains a significant gap in understanding disease pathogenesis. It was hypothesized that cytokine profiles from circulating T cells identify T cell subsets and T cell cytokines that define T2DM-associated inflammation.
Methods: Multiplex analyses were used to quantify T cell-associated cytokines in αCD3/αCD28-stimulated PBMCs, or B cell-depleted PBMCs, from subjects with T2DM or BMI-matched controls. Cytokine measurements were subjected to multivariate (principal component and partial least squares) analyses. Flow cytometry detected intracellular TNFα in multiple immune cell subsets in the presence/absence of antibodies that neutralize T cell cytokines.
Results: T cell cytokines were generally higher in T2DM samples, but Th17 cytokines are specifically important for classifying individuals correctly as T2DM. Multivariate analyses indicated that B cells support Th17 inflammation in T2DM but not control samples, while monocytes supported Th17 inflammation regardless of T2DM status. Partial least squares regression analysis indicated that both Th17 and Th1 cytokines impact %HbA1c.
Conclusions: Among various T cell subsets, Th17 cells are major contributors to inflammation and hyperglycemia and are uniquely supported by B cells in obesity-associated T2DM. |
| first_indexed | 2024-09-23T14:08:26Z |
| format | Article |
| id | mit-1721.1/106829 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T14:08:26Z |
| publishDate | 2017 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/1068292022-10-01T19:28:20Z Th17 cytokines differentiate obesity from obesity-associated type 2 diabetes and promote TNFα production Ip, Blanche Belkina, Anna C. DeFuria, Jason Jagannathan-Bogdan, Madhumita Zhu, Min Kuchibhatla, Ramya McDonnell, Marie E. Xiao, Qiang Kepler, Thomas B. Apovian, Caroline M. Nikolajczyk, Barbara S. Cilfone, Nicholas A. Lauffenburger, Douglas A Massachusetts Institute of Technology. Department of Biological Engineering Cilfone, Nicholas A. Lauffenburger, Douglas A Objective: T cell inflammation plays pivotal roles in obesity-associated type 2 diabetes (T2DM). The identification of dominant sources of T cell inflammation in humans remains a significant gap in understanding disease pathogenesis. It was hypothesized that cytokine profiles from circulating T cells identify T cell subsets and T cell cytokines that define T2DM-associated inflammation. Methods: Multiplex analyses were used to quantify T cell-associated cytokines in αCD3/αCD28-stimulated PBMCs, or B cell-depleted PBMCs, from subjects with T2DM or BMI-matched controls. Cytokine measurements were subjected to multivariate (principal component and partial least squares) analyses. Flow cytometry detected intracellular TNFα in multiple immune cell subsets in the presence/absence of antibodies that neutralize T cell cytokines. Results: T cell cytokines were generally higher in T2DM samples, but Th17 cytokines are specifically important for classifying individuals correctly as T2DM. Multivariate analyses indicated that B cells support Th17 inflammation in T2DM but not control samples, while monocytes supported Th17 inflammation regardless of T2DM status. Partial least squares regression analysis indicated that both Th17 and Th1 cytokines impact %HbA1c. Conclusions: Among various T cell subsets, Th17 cells are major contributors to inflammation and hyperglycemia and are uniquely supported by B cells in obesity-associated T2DM. National Institutes of Health (U.S.) (Grants R21DK089270, 5R21DE021154, R56 DK096525, R24DK090963, and U01CA182898) Boston University. Genome Science Institute Boston University. Hematology Training Program (Grant HL007501) National Institute of Diabetes and Digestive and Kidney Diseases (U.S.). Diabetic Complications Consortium Boston University. Immunology Training Program (Grant AI007309) United States. Army Research Office (Institute for Collaborative Biotechnologies. Grant W911NF-09-0001) 2017-02-02T18:56:45Z 2017-02-02T18:56:45Z 2015-11 2015-07 Article http://purl.org/eprint/type/JournalArticle 1930-7381 1930-739X http://hdl.handle.net/1721.1/106829 Ip, Blanche et al. “Th17 Cytokines Differentiate Obesity from Obesity-Associated Type 2 Diabetes and Promote TNFα Production: Th17 Cytokine Signature in T2DM.” Obesity 24.1 (2016): 102–112. en_US http://dx.doi.org/10.1002/oby.21243 Obesity Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Nature Publishing Group PMC |
| spellingShingle | Ip, Blanche Belkina, Anna C. DeFuria, Jason Jagannathan-Bogdan, Madhumita Zhu, Min Kuchibhatla, Ramya McDonnell, Marie E. Xiao, Qiang Kepler, Thomas B. Apovian, Caroline M. Nikolajczyk, Barbara S. Cilfone, Nicholas A. Lauffenburger, Douglas A Th17 cytokines differentiate obesity from obesity-associated type 2 diabetes and promote TNFα production |
| title | Th17 cytokines differentiate obesity from obesity-associated type 2 diabetes and promote TNFα production |
| title_full | Th17 cytokines differentiate obesity from obesity-associated type 2 diabetes and promote TNFα production |
| title_fullStr | Th17 cytokines differentiate obesity from obesity-associated type 2 diabetes and promote TNFα production |
| title_full_unstemmed | Th17 cytokines differentiate obesity from obesity-associated type 2 diabetes and promote TNFα production |
| title_short | Th17 cytokines differentiate obesity from obesity-associated type 2 diabetes and promote TNFα production |
| title_sort | th17 cytokines differentiate obesity from obesity associated type 2 diabetes and promote tnfα production |
| url | http://hdl.handle.net/1721.1/106829 |
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