Chemokine CCL28 induces apoptosis of decidual stromal cells via binding CCR3/CCR10 in human spontaneous abortion

Sun, Chongling; Zhang, Yuanyuan; Tang, Chuan-Ling; Wang, Songcun; Piao, Hailan; Yu, Tao; Zhu, Rui; Du, Meirong; Li, Da‐Jin

doi:10.1093/molehr/gat038

Cited by 25 publications

(21 citation statements)

References 50 publications

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“…36 37 We notably show that TNF-α is the common factor that drives CCL28 and CCR10 expression in blood vessels and RA monocytes, as such RA patients treated with anti-TNF blockers show an insignificant lower trend of CCL28 and CCR10 expression compared with those treated with DMARDs. The fact that CCL28 and CCR10 are modulated by overlapping inflammatory factors in the cell types in which they colocalise makes RA myeloid and endothelial cells very responsive to CCL28 signalling.…”

Section: Discussionmentioning

confidence: 73%

Characterising the expression and function of CCL28 and its corresponding receptor, CCR10, in RA pathogenesis

et al. 2014

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Objective This study was conducted to determine the expression pattern, regulation and function of CCL28 and CCR10 in rheumatoid arthritis (RA) pathogenesis. Methods Expression of CCL28 and CCR10 was assessed in RA compared to other arthritis synovial tissues (ST)s or fluids (SF)s by histology or ELISA. The factors modulating CCL28 and CCR10 expression were identified in RA myeloid and endothelial cells by ELISA, FACS and Western blotting. The mechanism by which CCL28 ligation promotes RA angiogenesis was examined in control or CCR10 knockdown endothelial cell chemotaxis and capillary formation. Results CCL28 and/or CCR10 expression levels were accentuated in STs or SFs of patients with joint disease compared to normal controls and they were predominately coexpressed in RA myeloid and endothelial cells. We show that protein expression of CCL28 and CCR10 was modulated by TNF-α and TLR4 ligation in RA monocytes and endothelial cells and by IL-6 stimulation in RA macrophages. Neutralization of CCL28 in RA SF or blockade of CCR10 on human endothelial progenitor cells (EPC)s significantly reduced SF induced endothelial migration and capillary formation, demonstrating that ligation of joint CCL28 to endothelial CCR10+ cells participates in RA angiogenesis. We uncovered that angiogenesis driven by ligation of CCL28 to CCR10 is linked to the ERK cascade as CCR10 knockdown cells exhibit dysfunctional CCL28 induced ERK signaling, chemotaxis and capillary formation. Conclusions The overexpression of CCL28 and CCR10 in RA ST and their contribution to EPC migration into the RA joints support CCL28/CCR10 cascade as a potential therapeutic target for RA.

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Section: Discussionmentioning

confidence: 73%

Characterising the expression and function of CCL28 and its corresponding receptor, CCR10, in RA pathogenesis

et al. 2014

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“…DSCs were isolated by collagenase IV/DNase-I digestion and discontinuous Percoll gradient centrifugation as our previously described4041. This method supplies a 99% purity of DSCs (Vimentin + CK7 − Smooth actin − Factor VIII − ).…”

Section: Methodsmentioning

confidence: 99%

Tim-3 protects decidual stromal cells from toll-like receptor-mediated apoptosis and inflammatory reactions and promotes Th2 bias at the maternal-fetal interface

Wang

Cao

Piao

et al. 2015

Sci Rep

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Toll-like receptors (TLRs) are important in mediating immune responses against various pathogens during pregnancy. However, uncontrolled TLR-triggered inflammation will endanger normal pregnancy, resulting in pregnancy loss. Therefore, maintenance of a moderate inflammatory response is crucial for successful pregnancy under conditions of infection. Here, we demonstrated significantly lowered expression of T-cell immunoglobulin and mucin domain 3 (Tim-3) in miscarried decidual stromal cells (DSCs), indicating that Tim-3 might play important roles in maintaining successful pregnancies. Activation of TLR signaling induced pro-inflammatory cytokine production and apoptosis of DSCs, which was accompanied by up-regulated Tim-3 expression. Tim-3, in turn, protected DSCs from TLR-mediated apoptosis in an ERK1/2 pathway-dependent manner. In addition, Tim-3 inhibited TLR signaling-induced inflammatory cytokine production by DSCs through suppressing NF-κB activation. Tim-3 increased production of T helper 2 (Th2)-type cytokines by DSCs and reversed the inhibitory effect of LPS on Th2 cytokine generation by up-regulation of interferon regulatory factor 4 expression. Tim-3 blockade abolished the effect of Tim-3 on the inflammatory response to LPS stimulation. Thus, Tim-3 signaling could represent a “self-control” mechanism in TLR-triggered inflammation during pregnancy. These findings identify Tim-3 as a key regulator of DSCs and suggest its potential as a target for the treatment of spontaneous abortion.

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“…More recently increased decidual stromal cell secreted levels of TNF have been reported in women with spontaneous miscarriage (Sun et al, 2013).…”

Section: Tnf-αmentioning

confidence: 99%

“…Several other cytokines, such as IL-2, IL-1β, IL-17A, have also been shown to be dysregulated in the decidua of women miscarriage (Sun et al, 2013;Garzia et al, 2013). However, their roles in establishment of pregnancy have not been well defined, although they do play roles in immune responses.…”

Section: Other Cytokinesmentioning

confidence: 99%

Decidual cytokines and pregnancy complications: focus on spontaneous miscarriage

Lash

Ernerudh

2015

Journal of Reproductive Immunology

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The establishment of pregnancy requires the co-ordinated implantation of the embryo into the receptive decidua, placentation, trophoblast invasion of the maternal decidua and myometrium in addition to remodelling of the uterine spiral arteries. Failure of any of these steps can lead to a range of pregnancy complications, including miscarriage, pre-eclampsia, fetal growth restriction, placenta accreta and pre-term birth. Cytokines are small multifunctional proteins often derived from leucocytes and have primarily been described through their immunomodulatory actions. The maternal-fetal interface is considered to be immunosuppressed to allow development of the semi-allogeneic placental fetal unit. However, cytokine profiles of the decidua and different decidual cell types suggest that the in vivo situation might be more complex. Data suggest that decidual-derived cytokines not only play roles in immunosuppression, but also in other aspects of the establishment of pregnancy, including the regulation of trophoblast invasion and spiral artery remodelling. This review focuses on the potential role of decidua-derived cytokines in the aetiology of unexplained spontaneous miscarriage. (C) 2015 Elsevier Ireland Ltd. All rights reserved

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Chemokine CCL28 induces apoptosis of decidual stromal cells via binding CCR3/CCR10 in human spontaneous abortion

Cited by 25 publications

References 50 publications

Characterising the expression and function of CCL28 and its corresponding receptor, CCR10, in RA pathogenesis

Characterising the expression and function of CCL28 and its corresponding receptor, CCR10, in RA pathogenesis

Tim-3 protects decidual stromal cells from toll-like receptor-mediated apoptosis and inflammatory reactions and promotes Th2 bias at the maternal-fetal interface

Decidual cytokines and pregnancy complications: focus on spontaneous miscarriage

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