Shadi Eghbal-Fard1,2, Mehdi Yousefi3,4, Hanieh Heydarlou3, Majid Ahmadi3, Simin Taghavi5, Aliakbar Movasaghpour6, Farhad Jadidi-Niaragh3,4, Bahman Yousefi7, Sanam Dolati4, Mohammad Hojjat-Farsangi8, Reza Rikhtegar4, Mohammad Nouri1, Leili Aghebati-Maleki9. 1. Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. 2. Student's Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran. 3. Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. 4. Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran. 5. Women's Reproductive Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. 6. Hematology & Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. 7. Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. 8. Department of Oncology-Pathology, Immune and Gene Therapy Lab, Cancer Center Karolinska (CCK), Karolinska University Hospital Solna and Karolinska Institute, Stockholm, Sweden. 9. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Abstract
PROBLEM: Inappropriate activation of the immune system, particularly the imbalance of T-helper type 17 (Th17)/regulatory T (Treg) cells is thought to play considerable roles in preeclampsia (PE). To investigate the probable effects of the adaptive immune system in the pathophysiology of PE, we analyzed the dynamic changes of Th17/Treg cells, cytokines profile, and transcription pattern of Th17/Treg-related genes and microRNAs (miRNAs) in 50 women suffering from PE in comparison with 50 healthy pregnant women. METHODS: Expressions of cytokines, specific transcription factors, and related miRNAs were measured by real-time polymerase chain reaction (PCR). Enzyme-linked immunosorbent assay (ELISA) was used to test the interleukin (IL)-17, IL-23, IL-6, and IL-10 and transforming growth factor β in serum and supernatant of peripheral blood mononuclear cells (PBMCs). The frequency of Th17 and Treg cells were determined by flow cytometry. RESULTS: PE patients exhibited a decreased number of Treg cells (p = 0.006), while Th17 cells were increased ( p = 0.004). Forkhead box P3 and IL-10 mRNA expressions were reduced ( p = 0.0001 and 0.0028, respectively), while expressions of retinoic acid receptor-related orphan nuclear receptor γt, IL-17, IL-23, and IL-6 were enhanced ( p < 0.0001, 0.0018, 0.0014, and 0.027, respectively). ELISA results also showed increased levels of IL-6, IL-17, and IL-23 ( p = 0.022, 0.0005, 0.0081, respectively), and decreased levels of IL-10 in the supernatant of PBMCs of PE patients compared with control group ( p = 0.0011). There was significant upregulation of miR-106b and miR-326 ( p = 0.0048 and 0.028, respectively) in PE patients in comparison with the control group. CONCLUSIONS: These findings suggest that imbalance of Th17/Treg cells, regulated possibly via microRNAs, may be involved in the pathogenesis of PE, emphasizing on the importance of these cells in feto-maternal immune cross-talk.
PROBLEM: Inappropriate activation of the immune system, particularly the imbalance of T-helper type 17 (Th17)/regulatory T (Treg) cells is thought to play considerable roles in preeclampsia (PE). To investigate the probable effects of the adaptive immune system in the pathophysiology of PE, we analyzed the dynamic changes of Th17/Treg cells, cytokines profile, and transcription pattern of Th17/Treg-related genes and microRNAs (miRNAs) in 50 women suffering from PE in comparison with 50 healthy pregnant women. METHODS: Expressions of cytokines, specific transcription factors, and related miRNAs were measured by real-time polymerase chain reaction (PCR). Enzyme-linked immunosorbent assay (ELISA) was used to test the interleukin (IL)-17, IL-23, IL-6, and IL-10 and transforming growth factor β in serum and supernatant of peripheral blood mononuclear cells (PBMCs). The frequency of Th17 and Treg cells were determined by flow cytometry. RESULTS: PE patients exhibited a decreased number of Treg cells (p = 0.006), while Th17 cells were increased ( p = 0.004). Forkhead box P3 and IL-10 mRNA expressions were reduced ( p = 0.0001 and 0.0028, respectively), while expressions of retinoic acid receptor-related orphan nuclear receptor γt, IL-17, IL-23, and IL-6 were enhanced ( p < 0.0001, 0.0018, 0.0014, and 0.027, respectively). ELISA results also showed increased levels of IL-6, IL-17, and IL-23 ( p = 0.022, 0.0005, 0.0081, respectively), and decreased levels of IL-10 in the supernatant of PBMCs of PE patients compared with control group ( p = 0.0011). There was significant upregulation of miR-106b and miR-326 ( p = 0.0048 and 0.028, respectively) in PE patients in comparison with the control group. CONCLUSIONS: These findings suggest that imbalance of Th17/Treg cells, regulated possibly via microRNAs, may be involved in the pathogenesis of PE, emphasizing on the importance of these cells in feto-maternal immune cross-talk.
Authors: Mark W Cunningham; Lorena M Amaral; Nathan E Campbell; Denise C Cornelius; Tarek Ibrahim; Venkata Ramana Vaka; Babbette LaMarca Journal: Biol Sex Differ Date: 2021-01-06 Impact factor: 5.027
Authors: Hossam El-Sheikh Ali; Shavahn C Loux; Laura Kennedy; Kirsten E Scoggin; Pouya Dini; Carleigh E Fedorka; Theodore S Kalbfleisch; Alejandro Esteller-Vico; David W Horohov; Erdal Erol; Craig N Carter; Jackie L Smith; Barry A Ball Journal: Vet Res Date: 2021-07-08 Impact factor: 3.683