Possible involvement of crosstalk between endometrial cells and mast cells in the development of endometriosis via CCL8/CCR1

Li, Tiantian; Wang, Jianzhang; Guo, Xinyue; Qin, Yu; Ding, Shaojie; Xu, Xinxin; Peng, Yangying; Zhu, Libo; Zou, Gen; Zhang, Xinmei

doi:10.1016/j.biopha.2020.110476

Cited by 31 publications

(17 citation statements)

References 56 publications

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“…99 One target that may be of interest is the chemokine CCL8, which was upregulated in mast cells upon co-culture with endometrial cells and also increased the proliferation and migration of endometrial epithelial cells. 100 Expression of CCL8 and its receptor CCR1 were overexpressed in the ectopic endometrium, where it was co-localized with blood vessels, a finding which confirms earlier reports of high concentrations of mast cells around blood vessels in lesions 101 and inhibition of CCR1 attenuated angiogenesis in a mouse model of endometriosis. 100 Additional mast cell targets that may be of interest in treating endometriosis include Janus Kinase 3 (JAK3) which is highly expressed in both murine and human mast cell and plays a key role in IgE-mediated cell degranulation.…”

Section: Mast Cellssupporting

confidence: 85%

“…100 Expression of CCL8 and its receptor CCR1 were overexpressed in the ectopic endometrium, where it was co-localized with blood vessels, a finding which confirms earlier reports of high concentrations of mast cells around blood vessels in lesions 101 and inhibition of CCR1 attenuated angiogenesis in a mouse model of endometriosis. 100 Additional mast cell targets that may be of interest in treating endometriosis include Janus Kinase 3 (JAK3) which is highly expressed in both murine and human mast cell and plays a key role in IgE-mediated cell degranulation. 102 Indeed, JAK3 inhibitors have shown early promise in several pre-clinical inflammatory models including peritonitis, colitis, and airway inflammation.…”

Section: Mast Cellssupporting

confidence: 85%

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The role of peripheral nerve signaling in endometriosis

et al. 2021

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A hallmark of endometriosisa chronic debilitating condition whose causes are poorly understoodis neuronal innervation of lesions. Recent evidence demonstrates that the peripheral nervous system plays an important role in the pathophysiology of this disease. Sensory nerves, which surround and innervate endometriotic lesions, not only drive the chronic and debilitating pain associated with endometriosis but also contribute to a pro-growth phenotype by secreting neurotrophic factors and interacting with surrounding immune cells. The diverse array of contributions that neurons play in endometriosis indicate that it should be considered as a nerve-centric disease. This review is focused on the emerging field of exoneural biology and how it applies to the field of endometriosis, in particular the role that peripheral nerves play in driving and maintaining endometriotic lesions. A better understanding of the mechanisms of neuronal contribution to endometriosis, as well as their interactions with accompanying stromal and immune cells, will unearth novel disease-relevant pathways and targets, providing additional, more selective therapeutic horizons.

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Section: Mast Cellssupporting

confidence: 85%

Section: Mast Cellssupporting

confidence: 85%

The role of peripheral nerve signaling in endometriosis

et al. 2021

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“…Bilateral ovariectomy was performed 7 days before endometriosis induction, followed by subcutaneous injection of 0.5 mg estradiol benzoate dissolved in 60 mL corn oil every 5 days. Induction of endometriosis was performed as reported previously (25). The uterine horns of donors were dissected and cut into fragments <1mm 3 .…”

Section: Animalsmentioning

confidence: 99%

NLRP3 Inflammasome Activation of Mast Cells by Estrogen via the Nuclear-Initiated Signaling Pathway Contributes to the Development of Endometriosis

Guo

et al. 2021

Front. Immunol.

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Endometriosis is an estrogen-dependent gynecological disease. The pathogenesis of endometriosis remains controversial, although it is generally accepted that the inflammatory immune response plays a crucial role in this process. Mast cells (MCs) are multifunctional innate immune cells that accumulate in endometriotic lesions. However, the molecular mechanism by which estrogen modulates MCs in the development of endometriosis is not well understood. Here we report that estrogen can induce the expression of NOD-like receptor family pyrin domain containing 3 (NLRP3) through estrogen receptor (ER)-α via the estrogen responsive element (ERE) in MCs. Such transcriptional regulation is necessary for the activation of NLRP3 inflammasome and the production of mature interleukin (IL)-1β in MCs. Targeted inhibition of NLRP3 significantly restrained lesion progression and fibrogenesis in a mouse model of endometriosis. Collectively, these findings suggest that MCs contribute to the development of endometriosis through NLRP3 inflammasome activation mediated by nuclear-initiated estrogen signaling pathway.

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“…C3a present in the EM-PF can act, through C3aR interaction, which is abundantly expressed on the MCs present in the EM tissue (10,36). C3a involvement in EM has also been suggested by previous evidence highlighting its correlation with chemokine CCL8 (60), a promotor of the cross-talk between endometrial cells and MCs in the development of EM through the binding to its receptor CCR1, characterized by over-expression in the ectopic endometrium and colocalization with blood vessels in ovarian endometriomas (61).…”

Section: Discussionmentioning

confidence: 65%

The Inflammatory Feed-Forward Loop Triggered by the Complement Component C3 as a Potential Target in Endometriosis

et al. 2021

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The complement system is a major component of humoral innate immunity, acting as a first line of defense against microbes via opsonization and lysis of pathogens. However, novel roles of the complement system in inflammatory and immunological processes, including in cancer, are emerging. Endometriosis (EM), a benign disease characterized by ectopic endometrial implants, shows certain unique features of cancer, such as the capacity to invade surrounding tissues, and in severe cases, metastatic properties. A defective immune surveillance against autologous tissue deposited in the peritoneal cavity allows immune escape for endometriotic lesions. There is evidence that the glandular epithelial cells found in endometriotic implants produce and secrete the complement component C3. Here, we show, using immunofluorescence and RT-qPCR, the presence of locally synthesized C3 in the ectopic endometriotic tissue, but not in the eutopic tissue. We generated a murine model of EM via injection of minced uterine tissue from a donor mouse into the peritoneum of recipient mice. The wild type mice showed greater amount of cyst formation in the peritoneum compared to C3 knock-out mice. Peritoneal washings from the wild type mice with EM showed more degranulated mast cells compared to C3 knock-out mice, consistent with higher C3a levels in the peritoneal fluid of EM patients. We provide evidence that C3a participates in an auto-amplifying loop leading to mast cell infiltration and activation, which is pathogenic in EM. Thus, C3 can be considered a marker of EM and its local synthesis can promote the engraftment of the endometriotic cysts.

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Possible involvement of crosstalk between endometrial cells and mast cells in the development of endometriosis via CCL8/CCR1

Cited by 31 publications

References 56 publications

The role of peripheral nerve signaling in endometriosis

The role of peripheral nerve signaling in endometriosis

NLRP3 Inflammasome Activation of Mast Cells by Estrogen via the Nuclear-Initiated Signaling Pathway Contributes to the Development of Endometriosis

The Inflammatory Feed-Forward Loop Triggered by the Complement Component C3 as a Potential Target in Endometriosis

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