PD-1/PD-L1 regulates Treg differentiation in pregnancy-induced hypertension

Jiang, Lai; Tang, Chaoliang; Gong, Yanping; Liu, Yujie; Rao, J. V.; Chen, Su-Yu; Qu, Wanjun; Wu, Dexiang; Lei, Lei; Chen, Ling

doi:10.1590/1414-431x20187334

Cited by 22 publications

(10 citation statements)

References 33 publications

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“…Treg deficiency is also closely associated with the development of PIH . Compared with normal pregnant women, PD‐1 positive Treg cells significantly increased in women with PIH . Higher frequency of Treg cells with PD‐1 expression was also found in pre‐eclamptic women .…”

Section: Introductionmentioning

confidence: 93%

Immune checkpoint molecules in pregnancy: Focus on regulatory T cells

Zhang

Sun

2020

Eur J Immunol

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Regulatory T (Treg) cells are a specialized subpopulation of T cells that plays critical roles in the maintenance of immune homeostasis. Although efforts have been done, their role in human pregnancy is not fully understood. Numerous studies reported the presence of Treg cells throughout gestation by promoting maternal-fetal tolerance and fetal development. Furthermore, Treg population is heterogeneous as it is expressing different immune checkpoint molecules favoring immune suppressive function. Therefore, better understanding of the heterogeneity and function of Treg cells during pregnancy is critical for an effective immune intervention. Latest evidence has shown that several immune checkpoint molecules are closely associated with pregnancy outcome via multiple inhibitory mechanisms. Majority of these studies demonstrated the modulatory effects of immune checkpoint molecules on effector T-cell immunity, but their effects onTreg activation and function are still an enigma. In this review, we emphasize the potential influence of multiple immune checkpoint molecules, including CTLA-4, PD-1, Tim-3, LAG-3, and TIGIT, either in membrane or soluble form, on the function of decidual and peripheral Treg cells during pregnancy. Additionally, we discuss the promising future of targeting Treg cells via immune checkpoint molecules for pregnancy maintenance and prevention of complicated pregnancies.Keywords: CTLA-4 r PD-1 r pregnancy r Tim-3 r Treg cells

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Section: Introductionmentioning

confidence: 93%

Immune checkpoint molecules in pregnancy: Focus on regulatory T cells

Zhang

Sun

2020

Eur J Immunol

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“…Another research group showed a similar elevation of PD-L1 in Tregs from preeclampsia patients, although the percentages of Tregs and Treg-related cytokines, such as TGF-β, IL-10, and IL-3, were decreased. Furthermore, the aberrant differentiation of Tregs can be rectified by the PD-1/PD-L1 activator PD-L1 Fc, which indicates a potential therapeutic value of the PD-1/PD-L1 pathway for patients with preeclampsia (59). In preeclamptic rats, the protective effect of PD-L1 Fc is realized by reversing the Treg/Th17 cell imbalance and placental damage (60).…”

Section: B7-h1 and B7-dcmentioning

confidence: 99%

The Role of B7 Family Molecules in Maternal–Fetal Immunity

2020

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Pregnancy is a complex but well-arranged process, and a healthy fetus requires immune privilege and surveillance in the presence of paternally derived antigens. Maternal and fetal cells interact at the maternal-fetal interface. The upregulation and downregulation of maternal immunity executed by the leukocyte population predominantly depend on the activity of decidual natural killer cells and trophoblasts and are further modulated by a series of duplex signals. The B7 family, which consists of B7-1, B7-2, B7-H1, B7-DC, B7-H2, B7-H3, B7-H4, B7-H5, BTNL2, B7-H6, and B7-H7, is one of the most characterized and widely distributed signaling molecule superfamilies and conducts both stimulatory and inhibitory signals through separate interactions. In particular, the roles of B7-1, B7-2, B7-H1, and their corresponding receptors in the progression of normal pregnancy and some pregnancy complications have been extensively studied. Together with the TCR-MHC complex, B7 and its receptors play a critical role in cell proliferation and cytokine secretion. Depending on this ligand-receptor crosstalk, the balance between the tolerance and rejection of the fetus is perfectly maintained. This review aims to provide an overview of the current knowledge of the B7 family and its functions in regulating maternal-fetal immunity through individual interactions.

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“…The PD-ligand 1 Fc increased Treg number and elevated TGF-β and IL-10 expression. The blocking of PD-L1 by using monoclonal antibody reversed this effect [111]. The suppression of Treg can be modulated by Nox2 [112].…”

Section: Introductionmentioning

confidence: 99%

Adaptive Immunity in Hypertension

Mikołajczyk

Guzik

2019

Curr Hypertens Rep

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Purpose of Review In recent years, a vast body of evidence has accumulated indicating the role of the immune system in the regulation of blood pressure and modulation of hypertensive pathology. Numerous cells of the immune system, both innate and adaptive immunity, have been indicated to play an important role in the development and maintenance of hypertension. The purpose of this review was to summarize the role of adaptive immunity in experimental models of hypertension (genetic, saltsensitive, and Angiotensin (Ang) II induced) and in human studies. In particular, the role of T and B cells is discussed. Recent Findings In response to hypertensive stimuli such as Ang II and high salt, T cells become pro-inflammatory and they infiltrate the brain, blood vessel adventitia and periadventitial fat, heart, and the kidney. Pro-inflammatory T cell-derived cytokines such as IFN-γ and TNF-α (from CD8+ and CD4+Th1) and IL-17A (from the γδ-T cell and CD4+Th17) exacerbate hypertensive responses mediating both endothelial dysfunction and cardiac, renal, and neurodegenerative injury. The modulation of adaptive immune activation in hypertension has been attributed to target organ oxidative stress that leads to the generation of neoantigens, including isolevuglandin-modified proteins. The role of adaptive immunity is sex-specific with much more pronounced mechanisms in males than that in females. Hypertension is also associated with B cell activation and production of autoantibodies (anti-Hsp70, anti-Hsp65, anti-Hsp60, anti-AT1R, anti-α1AR, and anti-β1AR). The hypertensive responses can be inhibited by T regulatory lymphocytes (Tregs) and their anti-inflammatory IL-10. Summary Adaptive immunity and its interface with innate mechanisms may represent valuable targets in the modulation of blood pressure, as well as hypertension-related residual risk.

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PD-1/PD-L1 regulates Treg differentiation in pregnancy-induced hypertension

Cited by 22 publications

References 33 publications

Immune checkpoint molecules in pregnancy: Focus on regulatory T cells

Immune checkpoint molecules in pregnancy: Focus on regulatory T cells

The Role of B7 Family Molecules in Maternal–Fetal Immunity

Adaptive Immunity in Hypertension

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