دورية أكاديمية
Leptin Promotes Greater Ki67 Expression in CD4 + T Cells From Obese Compared to Lean Persons Living With HIV.
| العنوان: | Leptin Promotes Greater Ki67 Expression in CD4 + T Cells From Obese Compared to Lean Persons Living With HIV. |
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| المؤلفون: | Fuseini H; Divison of Infectious Diseases, Vanderbilt University Medical Center, Nashville, TN, United States., Smith R; Tennessee Center for AIDS Research, Vanderbilt University Medical Center, Nashville, TN, United States., Nochowicz CH; Tennessee Center for AIDS Research, Vanderbilt University Medical Center, Nashville, TN, United States., Simmons JD; Tennessee Center for AIDS Research, Vanderbilt University Medical Center, Nashville, TN, United States., Hannah L; Division of Diabetes, Endocrinology and Metabolism, Vanderbilt University Medical Center, Nashville, TN, United States., Wanjalla CN; Divison of Infectious Diseases, Vanderbilt University Medical Center, Nashville, TN, United States.; Tennessee Center for AIDS Research, Vanderbilt University Medical Center, Nashville, TN, United States., Gabriel CL; Tennessee Center for AIDS Research, Vanderbilt University Medical Center, Nashville, TN, United States.; Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University Medical Center, Nashville, TN, United States., Mashayekhi M; Division of Diabetes, Endocrinology and Metabolism, Vanderbilt University Medical Center, Nashville, TN, United States., Bailin SS; Divison of Infectious Diseases, Vanderbilt University Medical Center, Nashville, TN, United States., Castilho JL; Divison of Infectious Diseases, Vanderbilt University Medical Center, Nashville, TN, United States., Hasty AH; Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN, United States.; The Veterans Affairs Tennessee Healthcare System, Nashville, TN, United States., Koethe JR; Divison of Infectious Diseases, Vanderbilt University Medical Center, Nashville, TN, United States.; Tennessee Center for AIDS Research, Vanderbilt University Medical Center, Nashville, TN, United States.; The Veterans Affairs Tennessee Healthcare System, Nashville, TN, United States., Kalams SA; Divison of Infectious Diseases, Vanderbilt University Medical Center, Nashville, TN, United States.; Tennessee Center for AIDS Research, Vanderbilt University Medical Center, Nashville, TN, United States. |
| المصدر: | Frontiers in immunology [Front Immunol] 2022 Jan 17; Vol. 12, pp. 796898. Date of Electronic Publication: 2022 Jan 17 (Print Publication: 2021). |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [Lausanne : Frontiers Research Foundation] |
| مواضيع طبية MeSH: | Gene Expression*, CD4-Positive T-Lymphocytes/*drug effects , CD4-Positive T-Lymphocytes/*metabolism , HIV Infections/*genetics , Ki-67 Antigen/*metabolism , Leptin/*pharmacology , Obesity/*metabolism, Adult ; Biomarkers ; Body Mass Index ; CD4-Positive T-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/virology ; Cytokines/metabolism ; Female ; Flow Cytometry ; HIV Infections/virology ; Humans ; Ki-67 Antigen/genetics ; Leukocytes, Mononuclear/immunology ; Leukocytes, Mononuclear/metabolism ; Lymphocyte Activation ; Lymphocyte Count ; Male ; Middle Aged ; Obesity/genetics |
| مستخلص: | 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/m 2 , 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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Fuseini, Smith, Nochowicz, Simmons, Hannah, Wanjalla, Gabriel, Mashayekhi, Bailin, Castilho, Hasty, Koethe and Kalams.) |
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| معلومات مُعتمدة: | KL2 TR002245 United States TR NCATS NIH HHS; UL1 RR024975 United States RR NCRR NIH HHS; K23 AI120875 United States AI NIAID NIH HHS; K23 AI100700 United States AI NIAID NIH HHS; R01 DK112262 United States DK NIDDK NIH HHS; R25 HL145817 United States HL NHLBI NIH HHS; T32 HL007444 United States HL NHLBI NIH HHS; P30 AI110527 United States AI NIAID NIH HHS |
| فهرسة مساهمة: | Keywords: CD4+ T cell; HIV; IL-17A; Ki67; body mass index; leptin; obesity |
| المشرفين على المادة: | 0 (Biomarkers) 0 (Cytokines) 0 (Ki-67 Antigen) 0 (Leptin) |
| تواريخ الأحداث: | Date Created: 20220203 Date Completed: 20220224 Latest Revision: 20240608 |
| رمز التحديث: | 20240608 |
| مُعرف محوري في PubMed: | PMC8801429 |
| DOI: | 10.3389/fimmu.2021.796898 |
| PMID: | 35111163 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1664-3224 |
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| DOI: | 10.3389/fimmu.2021.796898 |