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Activated γδ T Cells With Higher CD107a Expression and Inflammatory Potential During Early Pregnancy in Patients With Recurrent Spontaneous Abortion.

ABSTRACT: Previous studies have reported the involvement of γδ T cells in recurrent spontaneous abortion (RSA); however, both pathogenic and protective effects were suggested. To interrogate the role of γδ T cells in RSA, peripheral blood from RSA patients and healthy women with or without pregnancy were analyzed for γδ T cells by flow cytometry (n = 9-11 for each group). Moreover, the decidua from pregnant RSA patients and healthy controls (RSA-P and HC-P group, respectively) was simultaneously stained for γδ T cells by immunohistochemistry (IHC) and bulk sequenced for gene expression. Our results demonstrated that the frequencies of peripheral γδ T cells and their subpopulations in RSA patients were comparable to that in healthy subjects, but the PD1 expression on Vδ2⁺ cells was increased in pregnant patients. Furthermore, peripheral Vδ2⁺ cells in RSA-P patients demonstrated significantly increased expression of CD107a, as compared to that in pregnant healthy controls. In addition, RSA-P patients had higher proportion of IL-17A-secreting but not IL-4-secreting Vδ2⁺ cells compared to the control groups. In decidua, an inflammatory microenvironment was also evident in RSA-P patients, in which CCL8 expression and the infiltration of certain immune cells were higher than that in the HC-P group, as revealed by transcriptional analysis. Finally, although the presence of γδ T cells in decidua could be detected during pregnancy in both RSA patients and healthy subjects by multicolor IHC analysis, the expression of CD107a on γδ T cells was markedly higher in the RSA-P group. Collectively, our results indicated that the increased activation, cytotoxicity, and inflammatory potential of peripheral and/or local γδ T cells might be responsible for the pathogenesis of RSA. These findings could provide a better understanding of the role of γδ T cells in RSA and shed light on novel treatment strategies by targeting γδ T cells for RSA patients.

SUBMITTER: Yu L

PROVIDER: S-EPMC8416064 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe etiology of recurrent spontaneous abortion (RSA) remains elusive despite specific investigations affirming the association between RSA and thyroid autoimmunity (TAI). This study explores the immunological and metabolic profiles of RSA patients exhibiting positive thyroid antibodies and their connection with the rates of first-trimester miscarriage and live births. The aim is to provide further guidance for clinical interventions.MethodsA retrospective analysis included 478 women with RSA. Thyroid profile, thyroid peroxidase antibodies, and anti-thyroglobulin antibodies were measured in all participants. The clinical characteristics and pregnancy outcomes of RSA women were compared between thyroid autoimmunity (TAI)-positive and TAI-negative patients. Significant factors associated with adverse pregnancy outcomes and risk prediction models were explored in TAI-positive patients. Correlation analysis was used to identify specific metabolic or immune biomarkers associated with thyroid autoantibodies.ResultsThe prevalence of TAI was 18.6%. Compared with women without TAI, the thyroid-stimulating hormone (TSH) concentration of TAI-positive RSA was significantly higher (2.80 ± 2.98 vs 1.89 ± 1.17, p=0.006). After 28 weeks, the live birth rate of the TAI-positive group was lower than that of the TAI-negative group, with statistical significance (p<0.05). The immune biomarkers that differed between RSA women with live births and those with first-trimester miscarriages were complement C4 and interleukin-6, respectively, in TAI-negative and TAI-positive women. Then, a risk prediction model for first-trimester miscarriage was constructed for TAI-positive women with an AUC of 0.81. Finally, some factors related to thyroid peroxidase antibody (TPO-Ab) levels were explored, and it was found that TPO-Ab levels were positively correlated with free thyroxine and negatively correlated with 25 hydroxyvitamin D, interleukin-4, and fasting blood glucose in RSA patients.ConclusionTAI-positive RSA patients have higher first-trimester miscarriage rates and a lower live birth rate, which may be related to metabolic immune shifts in TAI-positive RSA patients.

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Activated γδ T Cells With Higher CD107a Expression and Inflammatory Potential During Early Pregnancy in Patients With Recurrent Spontaneous Abortion.

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