Interleukin 23 regulates the functions of human decidual immune cells during early pregnancy.

BACKGROUND: This study investigated the effects of interleukin 23 (IL-23) on the production of cytokines (IL-1, IL-4, IL-10, and IL-17), the differentiation of Treg/Th17 and STAT3 (i.e., signal transducer and activator of transcription 3) in human decidual immune cells (DICs) during early pregnancy. METHODS: DICs were treated with recombinant human IL-23 and an antibody against IL-23 subunit p19. The differentiation of Treg and Th17 cells was detected by flow cytometry. Levels of IL-23 receptor (IL-23R), STAT3, and phosphorylated STAT3 (pSTAT3) was examined by Western blot. The production of IL1, IL4, IL10, and IL-17 in DICs was measured by ELISA. RESULTS: Exogenous recombinant human IL-23 significantly promoted the differentiation of Th17 cells from DICs, while anti-IL-23 antibody significantly promoted the differentiation of Treg cells from DICs. Consistent with the differentiation of Th17 and Tregs cells, levels of IL-1ß and IL-17 correlated positively with IL-23 treatment, and anti-IL-23 antibody increased the secretion of IL-4 and IL-10 from DICs. Levels of pSTAT3, but not STAT3 or IL-23R, were significantly elevated by recombinant IL-23 treatment; anti-IL-23 antibody significantly decreased the levels of pSTAT3 and IL-23R in DICs. CONCLUSIONS: IL-23 mediates the differentiation of Th17 and Treg cells and the production of associated cytokines in DICs. The potential mechanism likely involves the STAT3 pathway.

Recurrent Implantation Failure May Be Identified by a Combination of Diagnostic Biomarkers: An Analysis of Peripheral Blood Lymphocyte Subsets.

Background: Recurrent implantation failure (RIF) is a challenge during assisted reproductive technology (ART). In the present study, potential diagnostic biomarkers for the immune status of peripheral blood lymphocyte subsets in patients with RIF were analyzed, with the aim of identifying novel biomarkers that may predict RIF. Methods: A total of 41 participants, including 21 women with RIF and 20 fertile controls, were included in the present study. Functional analysis was performed and the cytokine status of natural killer (NK), T, CD8+ T, T helper (Th), and γδ T cells which are lymphocyte subsets in peripheral blood was measured using flow cytometry. Binary logistic regression analysis adjusted for T follicular helper 1 (Tfh1), Tfh2, Tfh17, and early NK cells was performed to determine the relationship between the peripheral blood lymphocyte subsets and RIF. Potential diagnostic biomarkers were assessed by logistic regression analysis and receiver operating characteristic curves. Results: There were significantly more Tfh1, Tfh17, and NK cells in the RIF group compared with the control group (all P < 0.05). However, the percentage of T, regulatory T (Tregs), and Tfh2 cells, as well as early inhibitory NK cells, was significantly lower in the RIF group compared with the control group (all P < 0.05). Following logistics regression analysis, Treg, Tfh17, and early inhibitory NK cells exhibited significant differences between the two groups. Combination diagnosis using these 3 biomarkers had a higher area under the curve of 0.900 (95% confidence interval: 0.808-0.992, P < 0.001) in the RIF group compared with that in the control group. Conclusion: T, Tregs, Tfh1, Tfh2, Tfh17, NK cells, and early inhibitory NK cells may play important regulatory roles in embryo implantation. The combination of 3 molecular markers (Treg, Tfh17, and early inhibitory NK cells) could provide a high diagnostic value for women with RIF, thus providing novel potential biomarkers for RIF in ART. The present findings could provide a reference either for the clinical treatment of patients with RIF or for future large, well-designed studies.

Prednisone may rebuild the immunologic homeostasis: Alteration of Th17 and Treg cells in the lymphocytes from rats' spleens after treated with prednisone-containing serum.

BACKGROUND: This study aimed to investigate alterations of T helper 17 (Th17), regulatory T (Treg) cells and relative cytokines after treating with prednisone-contained serum. Lymphocytes were isolated from female rats' spleens. METHODS: The splenic lymphocytes were divided into four groups: which were treated with normal rats' serum (control); prednisone-containing rats' serum (PDN); normal rats' serum and cytokines (CTK); cytokines and prednisone-containing rats' serum (PDN + CTK). The mRNA expression level of RORC, Foxp3 and interleukin-17 (IL-17) was examined by reverse transcription-polymerase chain reaction. The quantities of Th17 and Treg cells were tested by flow cytometry, and the concentrations of IL-17 and IL-10 were detected by enzyme-linked immunosorbent assay. RESULTS: Higher mRNA expression level of Foxp3, percentages of Treg/CD4+ , and concentrations of IL-10, lower mRNA expressions of RORC and IL-17, concentrations of IL-17 and percentages of Th17/CD4+ in PDN group were detected, compared with control group (all p < 0.01). Similar trend was detected in PDN + CTK group, compared with CTK group (all p < 0.01). CONCLUSION: Our results suggest that prednisone may rebuild the immunologic homeostasis and may be used in human diseases with changes in the imbalance immune system such as unexplained recurrent spontaneous abortion (URSA), hepatitis B infection, or other autoimmune diseases.

[The effects of statins on the cerebral haemodynamics measured by transcranial Doppler in ischemic stroke patients].

OBJECTIVE: To evaluate the effects of statins on the cerebral haemodynamics of ischemic stroke patients with transcranial Doppler (TCD). METHODS: 70 inpatients with acute ischemic stroke were divided into two groups according whether they had taken statins after stroke. The change of the cerebral haemodynamics was studied in the two groups with TCD three months after stroke. RESULTS: Three months later, the systolic flow velocities and mean flow velocities of bilateral middle cerebral arteries in the statins groups significantly increased (P <0.05). The pulse index of bilateral middle cerebral arteries in statins group significantly decreased (P <0.05). The flow velocities and pulse index of bilateral middle cerebral arteries in control group don't change significantly (P > 0.05). CONCLUSIONS: Statins may have the effects of improving the situation of cerebral haemodynamics of patients with ischemic stroke.

Prednisone may induce immunologic tolerance by activating the functions of decidual immune cells in early pregnancy.

The objective of this study was to investigate alterations in human first-trimester decidual immune cells (DICs) and relevant cytokines after treatment with prednisone. Decidual lymphocytes were treated with prednisone alone, cytokines alone or the combination of prednisone and cytokines. Levels of STAT3, STAT5, RORC and FOXP3 mRNA were assayed using quantitative real-time PCR, proportions of CD4+ T helper 17 (Th17) and CD4+ T regulatory (Treg) cells were measured using flow cytometry, and concentrations of interleukin (IL)-17A and IL-10 were determined using enzyme-linked immunosorbent assay. After treatment with prednisone alone, levels of STAT5 and FOXP3 mRNA were significantly higher than in untreated control cells (both P < 0.01), while levels of RORC mRNA were significantly lower than in controls (P < 0.05). Levels of STAT3 mRNA did not vary significantly with treatment. After treatment with prednisone alone, proportions of Th17/CD4+ cells and levels of IL-17A were significantly lower than in control cells, and proportions of Treg/CD4+ cells and levels of IL-10 significantly higher than in controls (all P < 0.01). Our results suggest that prednisone may improve pregnancy outcomes by restoring immunological homeostasis through up-regulation of STAT5 and FOXP3, induction of DIC differentiation into Treg cells, inhibition of DIC differentiation into Th17 cells, reduction of IL-17A secretion and induction of IL-10 secretion.