Human pregnancy levels of estrogen and progesterone contribute to humoral immunity by activating T<sub>FH</sub>/B cell axis

Monteiro, Clarice; Kasahara, Taissa M.; Sacramento, Priscila M.; Dias, Aleida S.O.; Leite, Simone; Silva, Vander G.; Gupta, Sudhir; Agrawal, Anshu; Bento, Cleonice A.M.

doi:10.1002/eji.202048658

Cited by 17 publications

(18 citation statements)

References 90 publications

(147 reference statements)

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“…Females exhibit higher IgG antibody levels in the steady state and upon infection or vaccination exhibit higher IgG titers and numbers of memory and plasma B cells than males (11,154,155). Though this sex difference is in part likely due to effects of E2 on T cell help (156), seminal studies done in a murine DNA-specific BCR transgenic model have demonstrated that E2 has direct effects in breaking B cell tolerance [reviewed in Ref. (157)].…”

Section: Puberty Induces Thymic Involution and May Shift The Delicate...mentioning

confidence: 99%

Effect of puberty on the immune system: Relevance to multiple sclerosis

Ucciferri

Dunn

2022

Front. Pediatr.

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Puberty is a dynamic period marked by changing levels of sex hormones, the development of secondary sexual characteristics and reproductive maturity. This period has profound effects on various organ systems, including the immune system. The critical changes that occur in the immune system during pubertal onset have been shown to have implications for autoimmune conditions, including Multiple Sclerosis (MS). MS is rare prior to puberty but can manifest in children after puberty. This disease also has a clear female preponderance that only arises following pubertal onset, highlighting a potential role for sex hormones in autoimmunity. Early onset of puberty has also been shown to be a risk factor for MS. The purpose of this review is to overview the evidence that puberty regulates MS susceptibility and disease activity. Given that there is a paucity of studies that directly evaluate the effects of puberty on the immune system, we also discuss how the immune system is different in children and mice of pre- vs. post-pubertal ages and describe how gonadal hormones may regulate these immune mechanisms. We present evidence that puberty enhances the expression of co-stimulatory molecules and cytokine production by type 2 dendritic cells (DC2s) and plasmacytoid dendritic cells (pDCs), increases T helper 1 (Th1), Th17, and T follicular helper immunity, and promotes immunoglobulin (Ig)G antibody production. Overall, this review highlights how the immune system undergoes a functional maturation during puberty, which has the potential to explain the higher prevalence of MS and other autoimmune diseases seen in adolescence.

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Section: Puberty Induces Thymic Involution and May Shift The Delicate...mentioning

confidence: 99%

Effect of puberty on the immune system: Relevance to multiple sclerosis

Ucciferri

Dunn

2022

Front. Pediatr.

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“…A previous study also revealed an association between Tfh cells and human immunodeficiency virus (HIV) infection and showed that Tfh cells may play critical roles in antimicrobial defense, cancer, and autoimmunity (24,25). A recent study found that E2 and P4 cooperate in the humoral immune response by favoring the expansion of different cyclic Tfh cell subsets (26). No study has yet reported the relationship between Tfh cells and RIF.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2022

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BackgroundRecurrent 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.MethodsA 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.ResultsThere 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.ConclusionT, 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.

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“…Both costimulatory molecules, PD-1 and ICOS, are also expressed in peripheral, uterine and placental T follicular helper cells (Tfh). Tfh cells are pivotal to efficient humoral immunity and important for a successful pregnancy [ 69 , 70 , 71 ].…”

Section: Discussionmentioning

confidence: 99%

IL-10 Producing B Cells Protect against LPS-Induced Murine Preterm Birth by Promoting PD1- and ICOS-Expressing T Cells

Busse

Zenclussen

2022

Cells

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B cells and in particular IL-10-secreting B cells emerge as important players in immune balance during pregnancy. We have recently revealed that CD19-deficient (CD19−/−), B cell-specific IL-10-deficient (BIL-10−/−) and B cell-deficient µMT pregnant mice are highly susceptible to LPS-induced preterm birth (PTB). We aimed to analyze the ability of IL-10-secreting cells to protect from PTB and the underlying mechanisms. Wild type (WT), CD19−/−, BIL-10−/− and µMT mice were treated with LPS at gd16 and the cellular immune response was investigated 24 h later. LPS-treated BIL-10−/− dams showed a more pronounced PTB phenotype compared to WT, CD19−/− and µMT females, and increased inflammatory and reduced anti-inflammatory mediator concentrations in the peritoneal cavity and serum. CD19−/−, BIL-10−/− and µMT mice displayed altered immune cell population frequencies in the blood and uterus with lower numbers of IL-10-secreting B cells and T cells. BIL-10−/− mothers presented decreased frequencies of uterine CD4+CD25+Foxp3+ Treg cells. Co-stimulatory molecules are critical for feto-maternal tolerance and IL-10 secretion. We found dysregulated PD-1 expression in peripheral blood and ICOS expression in the uterus of CD19−/−, BIL-10−/− and µMT dams. Our data show that B cell-specific IL-10-signaling is essential for a balanced maternal immune response to an inflammatory stimulant that cannot be hampered without IL-10-secreting B cells.

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Human pregnancy levels of estrogen and progesterone contribute to humoral immunity by activating T_FH/B cell axis

Cited by 17 publications

References 90 publications

Effect of puberty on the immune system: Relevance to multiple sclerosis

Effect of puberty on the immune system: Relevance to multiple sclerosis

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

IL-10 Producing B Cells Protect against LPS-Induced Murine Preterm Birth by Promoting PD1- and ICOS-Expressing T Cells

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Human pregnancy levels of estrogen and progesterone contribute to humoral immunity by activating TFH/B cell axis

Cited by 17 publications

References 90 publications

Effect of puberty on the immune system: Relevance to multiple sclerosis

Effect of puberty on the immune system: Relevance to multiple sclerosis

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

IL-10 Producing B Cells Protect against LPS-Induced Murine Preterm Birth by Promoting PD1- and ICOS-Expressing T Cells

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Human pregnancy levels of estrogen and progesterone contribute to humoral immunity by activating T_FH/B cell axis