Role of Transforming Growth Factor-β1 in Regulating Fetal-Maternal Immune Tolerance in Normal and Pathological Pregnancy

Yang, Dongyong; Dai, Fangfang; Yuan, Mengqin; Zheng, Y.; Liu, Shiyi; Deng, Zhanfeng; Tan, Wei; Chen, Liping; Zhang, Qianjie; Zhao, Xiaomiao; Cheng, Yanxiang

doi:10.3389/fimmu.2021.689181

Cited by 38 publications

(40 citation statements)

References 115 publications

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“…Further, it also aids in angiogenesis, Treg production, balance between M1-M2 macrophage polarization and regulation of the NK cell function (Yang et al, 2021). In our study, we reported significantly increased (P < 0.05) mRNA expression of TGF-β1 in PBMCs of the pregnant cows.…”

Section: Discussionsupporting

confidence: 59%

“…The level of TGF-β1 has been reported to be higher in pregnant women, which revealed its potential regulatory function in fetal allograft survival in successful pregnancies (Ayatollahi et al, 2007). Further, it also aids in angiogenesis, Treg production, balance between M1-M2 macrophage polarization and regulation of the NK cell function (Yang et al, 2021). In our study, we reported significantly increased (P < 0.05) mRNA expression of TGF-β1 in PBMCs of the pregnant cows.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Indoleamine 2, 3-dioxygenase 1 mediated alterations in the functionality of immune cells, decipher the pregnancy outcomes in crossbred dairy cows

Mohapatra

Chaudhary

Panda

et al. 2022

Preprint

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Pregnancy establishment in bovines requires maternal immune cell modulation. Present study investigated possible role of immunosuppressive indolamine-2, 3-dioxygenase 1 (IDO1) enzyme in the alteration of neutrophil (NEUT) and peripheral blood mononuclear cells (PBMCs) functionality of crossbred cows. Blood was collected from non-pregnant (NP) and pregnant (P) cows, followed by isolation of NEUT and PBMCs. Plasma pro-inflammatory (IFNγ and TNFα) and anti-inflammatory cytokines (IL-4 and IL-10) were estimated by ELISA and analysis of IDO1 gene in NEUT and PBMCs by RT-qPCR. Neutrophil functionality was assessed by chemotaxis, measuring activity of myeloperoxidase and β-D glucuronidase enzyme and evaluating nitric oxide production. Changes in PBMCs functionality was determined by transcriptional expression of pro-inflammatory (IFNγ, TNFα) and anti-inflammatory cytokine (IL-4, IL-10, TGFβ1) genes. Significantly elevated (P < 0.05) anti-inflammatory cytokines, increased IDO1 expression, reduced NEUT velocity, MPO activity and NO production observed only in P cows. Significantly higher (P < 0.05) expression of anti-inflammatory cytokines and TNFα genes were observed in PBMCs. Study highlights possible role of IDO1 in modulating the immune cell and cytokine activity during early pregnancy and may be targeted as early pregnancy biomarkers.

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Section: Discussionsupporting

confidence: 59%

Section: Discussionmentioning

confidence: 99%

Indoleamine 2, 3-dioxygenase 1 mediated alterations in the functionality of immune cells, decipher the pregnancy outcomes in crossbred dairy cows

Mohapatra

Chaudhary

Panda

et al. 2022

Preprint

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“…Both LAP TGF-b1 and TGF-b have well-known immunosuppressive properties (37,38). TGF-b is a main inducer of Treg cell development and function, which are key elements in the immune modulation of both MS and pregnancy (39,40). However, since active TGF-b1 is difficult to measure, it is not optimal as a biomarker, and its broad biological effects complicate its use in treatment (41).…”

Section: Discussionmentioning

confidence: 99%

Plasma protein profiling reveals dynamic immunomodulatory changes in multiple sclerosis patients during pregnancy

et al. 2022

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Multiple sclerosis (MS) is a chronic autoimmune neuroinflammatory and neurodegenerative disorder of the central nervous system. Pregnancy represents a natural modulation of the disease course, where the relapse rate decreases, especially in the 3rd trimester, followed by a transient exacerbation after delivery. Although the exact mechanisms behind the pregnancy-induced modulation are yet to be deciphered, it is likely that the immune tolerance established during pregnancy is involved. In this study, we used the highly sensitive and specific proximity extension assay technology to perform protein profiling analysis of 92 inflammation-related proteins in MS patients (n=15) and healthy controls (n=10), longitudinally sampled before, during, and after pregnancy. Differential expression analysis was performed using linear models and p-values were adjusted for false discovery rate due to multiple comparisons. Our findings reveal gradual dynamic changes in plasma proteins that are most prominent during the 3rd trimester while reverting post-partum. Thus, this pattern reflects the disease activity of MS during pregnancy. Among the differentially expressed proteins in pregnancy, several proteins with known immunoregulatory properties were upregulated, such as PD-L1, LIF-R, TGF-β1, and CCL28. On the other hand, inflammatory chemokines such as CCL8, CCL13, and CXCL5, as well as members of the tumor necrosis factor family, TRANCE and TWEAK, were downregulated. Further in-depth studies will reveal if these proteins can serve as biomarkers in MS and whether they are mechanistically involved in the disease amelioration and worsening. A deeper understanding of the mechanisms involved may identify new treatment strategies mimicking the pregnancy milieu.

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“…Moreovere, an increase in TGF-β is observed, which is essential for the transition between the cell-mediated immune response to the humoral one [ 39 ]. In addition, there is an increase in HBD1 and HBD4, which is extremely interesting since the first is constitutively expressed in the genital tract [ 40 , 41 ], while the second is inducible in case of infections [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

Diagnostic and Therapeutic Potential for HNP-1, HBD-1 and HBD-4 in Pregnant Women with COVID-19

Brancaccio

Mennitti

Calvanese

et al. 2022

IJMS

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Pregnancy is characterized by significant immunological changes and a cytokine profile, as well as vitamin deficiencies that can cause problems for the correct development of a fetus. Defensins are small antimicrobial peptides that are part of the innate immune system and are involved in several biological activities. Following that, this study aims to compare the levels of various cytokines and to investigate the role of defensins between pregnant women with confirmed COVID-19 infection and pregnant women without any defined risk factor. TNF-α, TGF-β, IL-2 and IL-10, β-defensins, have been evaluated by gene expression in our population. At the same time, by ELISA assay IL-6, IL-8, defensin alpha 1, defensin beta 1 and defensin beta 4 have been measured. The data obtained show that mothers affected by COVID-19 have an increase in pro-inflammatory factors (TNF-α, TGF-β, IL-2, IL-6, IL-8) compared to controls; this increase could generate a sort of “protection of the fetus” from virus attacks. Contemporarily, we have an increase in the anti-inflammatory cytokine IL-10 and an increase in AMPs, which highlights how the mother’s body is responding to the viral attack. These results allow us to hypothesize a mechanism of “trafficking” of antimicrobial peptides from the mother to the fetus that would help the fetus to protect itself from the infection in progress.

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Role of Transforming Growth Factor-β1 in Regulating Fetal-Maternal Immune Tolerance in Normal and Pathological Pregnancy

Cited by 38 publications

References 115 publications

Indoleamine 2, 3-dioxygenase 1 mediated alterations in the functionality of immune cells, decipher the pregnancy outcomes in crossbred dairy cows

Indoleamine 2, 3-dioxygenase 1 mediated alterations in the functionality of immune cells, decipher the pregnancy outcomes in crossbred dairy cows

Plasma protein profiling reveals dynamic immunomodulatory changes in multiple sclerosis patients during pregnancy

Diagnostic and Therapeutic Potential for HNP-1, HBD-1 and HBD-4 in Pregnant Women with COVID-19

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