Leptin Promotes Greater Ki67 Expression in CD4+ T Cells From Obese Compared to Lean Persons Living With HIV
While antiretroviral therapy (ART) has proven effective in suppressing viremia and disease progression among people living with human immunodeficiency virus (HIV; PLWH), suboptimal CD4+ T cell reconstitution remains a major obstacle in nearly 30% of ART-treated individuals. Epidemiological studies d...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.796898/full |
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| author | Hubaida Fuseini Rita Smith Cindy H. Nochowicz Joshua D. Simmons LaToya Hannah Celestine N. Wanjalla Celestine N. Wanjalla Curtis L. Gabriel Curtis L. Gabriel Mona Mashayekhi Samuel S. Bailin Jessica L. Castilho Alyssa H. Hasty Alyssa H. Hasty John R. Koethe John R. Koethe John R. Koethe Spyros A. Kalams Spyros A. Kalams |
| author_facet | Hubaida Fuseini Rita Smith Cindy H. Nochowicz Joshua D. Simmons LaToya Hannah Celestine N. Wanjalla Celestine N. Wanjalla Curtis L. Gabriel Curtis L. Gabriel Mona Mashayekhi Samuel S. Bailin Jessica L. Castilho Alyssa H. Hasty Alyssa H. Hasty John R. Koethe John R. Koethe John R. Koethe Spyros A. Kalams Spyros A. Kalams |
| author_sort | Hubaida Fuseini |
| collection | DOAJ |
| description | While antiretroviral therapy (ART) has proven effective in suppressing viremia and disease progression among people living with human immunodeficiency virus (HIV; PLWH), suboptimal CD4+ T cell reconstitution remains a major obstacle in nearly 30% of ART-treated individuals. Epidemiological studies demonstrate that obesity, or a body mass index (BMI) ≥ 30 kg/m2, is positively correlated with greater CD4+ T cell recovery in PLWH on ART. Leptin is a known immunomodulator that is produced in proportion to fat mass and is increased in obese individuals, including PLWH. We hypothesized that CD4+ T cells from obese PLWH have increased cell proliferation and cytokine production compared to cells from lean PLWH, potentially modulated by differential effects of leptin signaling. To test this hypothesis, peripheral blood mononuclear cells from obese and lean PLWH with long-term virologic suppression on the same ART regimen were pretreated with recombinant leptin and then stimulated with anti-CD3/CD28 or PMA/ionomycin to measure Ki67 expression, leptin receptor (LepR) surface expression and cytokine production. In the absence of leptin, Ki67 expression and IL-17A production were significantly higher in CD4+ T cells from obese compared to lean PLWH. However, LepR expression was significantly lower on CD4+ T cells from obese compared to lean PLWH. After leptin treatment, Ki67 expression was significantly increased in CD4+ T cells from obese PLWH compared to the lean participants. Leptin also increased IL-17A production in CD4+ T cells from obese healthy controls. In contrast, leptin decreased IL-17A production in CD4+ T cells from both obese and lean PLWH. Combined, these results demonstrate that obesity is associated with greater CD4+ T cell proliferation among PLWH, and that higher circulating leptin levels in obesity may contribute to improved CD4+ T reconstitution in PLWH initiating ART. |
| first_indexed | 2024-12-24T01:45:04Z |
| format | Article |
| id | doaj.art-299ecc70912240898e96963bc847c13f |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-24T01:45:04Z |
| publishDate | 2022-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-299ecc70912240898e96963bc847c13f2022-12-21T17:21:54ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-01-011210.3389/fimmu.2021.796898796898Leptin Promotes Greater Ki67 Expression in CD4+ T Cells From Obese Compared to Lean Persons Living With HIVHubaida Fuseini0Rita Smith1Cindy H. Nochowicz2Joshua D. Simmons3LaToya Hannah4Celestine N. Wanjalla5Celestine N. Wanjalla6Curtis L. Gabriel7Curtis L. Gabriel8Mona Mashayekhi9Samuel S. Bailin10Jessica L. Castilho11Alyssa H. Hasty12Alyssa H. Hasty13John R. Koethe14John R. Koethe15John R. Koethe16Spyros A. Kalams17Spyros A. Kalams18Divison of Infectious Diseases, Vanderbilt University Medical Center, Nashville, TN, United StatesTennessee Center for AIDS Research, Vanderbilt University Medical Center, Nashville, TN, United StatesTennessee Center for AIDS Research, Vanderbilt University Medical Center, Nashville, TN, United StatesTennessee Center for AIDS Research, Vanderbilt University Medical Center, Nashville, TN, United StatesDivision of Diabetes, Endocrinology and Metabolism, Vanderbilt University Medical Center, Nashville, TN, United StatesDivison of Infectious Diseases, Vanderbilt University Medical Center, Nashville, TN, United StatesTennessee Center for AIDS Research, Vanderbilt University Medical Center, Nashville, TN, United StatesTennessee Center for AIDS Research, Vanderbilt University Medical Center, Nashville, TN, United StatesDivision of Gastroenterology, Hepatology and Nutrition, Vanderbilt University Medical Center, Nashville, TN, United StatesDivision of Diabetes, Endocrinology and Metabolism, Vanderbilt University Medical Center, Nashville, TN, United StatesDivison of Infectious Diseases, Vanderbilt University Medical Center, Nashville, TN, United StatesDivison of Infectious Diseases, Vanderbilt University Medical Center, Nashville, TN, United StatesDepartment of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN, United StatesThe Veterans Affairs Tennessee Healthcare System, Nashville, TN, United StatesDivison of Infectious Diseases, Vanderbilt University Medical Center, Nashville, TN, United StatesTennessee Center for AIDS Research, Vanderbilt University Medical Center, Nashville, TN, United StatesThe Veterans Affairs Tennessee Healthcare System, Nashville, TN, United StatesDivison of Infectious Diseases, Vanderbilt University Medical Center, Nashville, TN, United StatesTennessee Center for AIDS Research, Vanderbilt University Medical Center, Nashville, TN, United StatesWhile antiretroviral therapy (ART) has proven effective in suppressing viremia and disease progression among people living with human immunodeficiency virus (HIV; PLWH), suboptimal CD4+ T cell reconstitution remains a major obstacle in nearly 30% of ART-treated individuals. Epidemiological studies demonstrate that obesity, or a body mass index (BMI) ≥ 30 kg/m2, is positively correlated with greater CD4+ T cell recovery in PLWH on ART. Leptin is a known immunomodulator that is produced in proportion to fat mass and is increased in obese individuals, including PLWH. We hypothesized that CD4+ T cells from obese PLWH have increased cell proliferation and cytokine production compared to cells from lean PLWH, potentially modulated by differential effects of leptin signaling. To test this hypothesis, peripheral blood mononuclear cells from obese and lean PLWH with long-term virologic suppression on the same ART regimen were pretreated with recombinant leptin and then stimulated with anti-CD3/CD28 or PMA/ionomycin to measure Ki67 expression, leptin receptor (LepR) surface expression and cytokine production. In the absence of leptin, Ki67 expression and IL-17A production were significantly higher in CD4+ T cells from obese compared to lean PLWH. However, LepR expression was significantly lower on CD4+ T cells from obese compared to lean PLWH. After leptin treatment, Ki67 expression was significantly increased in CD4+ T cells from obese PLWH compared to the lean participants. Leptin also increased IL-17A production in CD4+ T cells from obese healthy controls. In contrast, leptin decreased IL-17A production in CD4+ T cells from both obese and lean PLWH. Combined, these results demonstrate that obesity is associated with greater CD4+ T cell proliferation among PLWH, and that higher circulating leptin levels in obesity may contribute to improved CD4+ T reconstitution in PLWH initiating ART.https://www.frontiersin.org/articles/10.3389/fimmu.2021.796898/fullleptinbody mass indexobesityHIVCD4+ T cellKi67 |
| spellingShingle | Hubaida Fuseini Rita Smith Cindy H. Nochowicz Joshua D. Simmons LaToya Hannah Celestine N. Wanjalla Celestine N. Wanjalla Curtis L. Gabriel Curtis L. Gabriel Mona Mashayekhi Samuel S. Bailin Jessica L. Castilho Alyssa H. Hasty Alyssa H. Hasty John R. Koethe John R. Koethe John R. Koethe Spyros A. Kalams Spyros A. Kalams Leptin Promotes Greater Ki67 Expression in CD4+ T Cells From Obese Compared to Lean Persons Living With HIV Frontiers in Immunology leptin body mass index obesity HIV CD4+ T cell Ki67 |
| title | Leptin Promotes Greater Ki67 Expression in CD4+ T Cells From Obese Compared to Lean Persons Living With HIV |
| title_full | Leptin Promotes Greater Ki67 Expression in CD4+ T Cells From Obese Compared to Lean Persons Living With HIV |
| title_fullStr | Leptin Promotes Greater Ki67 Expression in CD4+ T Cells From Obese Compared to Lean Persons Living With HIV |
| title_full_unstemmed | Leptin Promotes Greater Ki67 Expression in CD4+ T Cells From Obese Compared to Lean Persons Living With HIV |
| title_short | Leptin Promotes Greater Ki67 Expression in CD4+ T Cells From Obese Compared to Lean Persons Living With HIV |
| title_sort | leptin promotes greater ki67 expression in cd4 t cells from obese compared to lean persons living with hiv |
| topic | leptin body mass index obesity HIV CD4+ T cell Ki67 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.796898/full |
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