Insights into the role of complement system in the pathophysiology of endometriosis

Rahal, Danilo; Andrade, Fabiana Antunes; Nisihara, Renato

doi:10.1016/j.imlet.2021.01.005

Cited by 8 publications

(3 citation statements)

References 41 publications

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“…and IL8 is responsible of stimulating proliferation, migration, angiogenesis and immune suppression [26]. The dysregulation of complements was found and associated with the local chronic inflammation of endometriosis [27]. Therefore, the transformation of ectopic EMCs increasedly expressing cytokines and complements promoted the cellular activity and inflammatory response.…”

Section: Discussionmentioning

confidence: 99%

The dysfunction of CD8⁺ T cells triggered by endometriotic stromal cells promotes the immune survival of endometriosis

Huang,

Lin,

Zhang

et al. 2024

Immunology

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Endometriosis is defined as an oestrogen‐dependent and inflammatory gynaecological disease of which the pathogenesis remains unclear. This study aimed to investigate the cellular heterogeneity and reveal the effect of CD8+ T cells on the progress of endometriosis. Three ovarian endometriosis patients were collected, and single‐cell RNA sequencing (scRNA‐seq) progressed and delineated the cellular landscape of endometriosis containing five cell clusters. The endometrial cells (EMCs) were the major component, of which the mesenchymal cells were preponderant and characterized with increased inflammation and oestrogen synthesis in endometriosis. The proportion of T cells, mainly CD8+ T cells rather than CD4+, was reduced in endometriotic lesions, and the cytokines and cytotoxicity of ectopic T cells were depressed. CD8+ T cells depressed the proliferation of ESCs through inhibiting CDK1/CCNB1 pathway to arrest the cell cycle and triggered inflammation through activating STAT1 pathway. Correspondingly, the coculture with ESCs resulted in the dysfunction of CD8+ T cells through upregulating STAT1/PDCD1 pathway and glycolysis‐promoted metabolism reprogramming. The endometriotic lesions were larger in nude mouse models with T‐cell deficiency than the normal mouse models. The inhibition of T cells via CD90.2 or CD8A antibody increased the endometriotic lesions in mouse models, and the supplement of T cells to nude mouse models diminished the lesion sizes. In conclusion, this study revealed the global cellular variation of endometriosis among which the cellular count and physiology of EMCs and T cells were significantly changed. The depressed cytotoxicity and aberrant metabolism of CD8+ T cells were induced by ESCs with the activation of STAT1/PDCD1 pathway resulting in immune survival to promote endometriosis.

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Section: Discussionmentioning

confidence: 99%

The dysfunction of CD8⁺ T cells triggered by endometriotic stromal cells promotes the immune survival of endometriosis

Huang,

Lin,

Zhang

et al. 2024

Immunology

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“…Several complement components such as C3, C4A, C7, factor D, factor B, factor H, and mannose-associated serine protease 1 (MASP1), are differentially expressed in EM compared to normal uterine tissues ( 13 ). The most studied protein is C3 ( 34 ), although its contribution in EM pathogenic mechanisms has not been elucidated yet.…”

Section: Discussionmentioning

confidence: 99%

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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“…The complement system, recognized as the activating pathway of complements, constitutes a significant element within the innate immune system (Rahal et al, 2021). Initially, the prevailing belief was that the complement system's primary function lay in recognizing and eliminating pathogens exclusively through the stimulation of phagocytosis by immune cells (Killick et al, 2018).…”

Section: Targeting the Complement Activation Pathway: Therapeutic Imp...mentioning

confidence: 99%

Gut-immunity-joint axis: a new therapeutic target for gouty arthritis

Chen,

Luo,

et al. 2024

Front. Pharmacol.

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Gouty arthritis (GA) is an inflammatory disease characterized by pain. The primary goal of current treatment strategies during GA flares remains the reduction of inflammation and pain. Research suggests that the gut microbiota and microbial metabolites contribute to the modulation of the inflammatory mechanism associated with GA, particularly through their effect on macrophage polarization. The increasing understanding of the gut-joint axis emphasizes the importance of this interaction. The primary objective of this review is to summarize existing research on the gut-immune-joint axis in GA, aiming to enhance understanding of the intricate processes and pathogenic pathways associated with pain and inflammation in GA, as documented in the published literature. The refined comprehension of the gut-joint axis may potentially contribute to the future development of analgesic drugs targeting gut microbes for GA.

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Insights into the role of complement system in the pathophysiology of endometriosis

Cited by 8 publications

References 41 publications

The dysfunction of CD8⁺ T cells triggered by endometriotic stromal cells promotes the immune survival of endometriosis

The dysfunction of CD8⁺ T cells triggered by endometriotic stromal cells promotes the immune survival of endometriosis

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

Gut-immunity-joint axis: a new therapeutic target for gouty arthritis

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Insights into the role of complement system in the pathophysiology of endometriosis

Cited by 8 publications

References 41 publications

The dysfunction of CD8+ T cells triggered by endometriotic stromal cells promotes the immune survival of endometriosis

The dysfunction of CD8+ T cells triggered by endometriotic stromal cells promotes the immune survival of endometriosis

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

Gut-immunity-joint axis: a new therapeutic target for gouty arthritis

Contact Info

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The dysfunction of CD8⁺ T cells triggered by endometriotic stromal cells promotes the immune survival of endometriosis

The dysfunction of CD8⁺ T cells triggered by endometriotic stromal cells promotes the immune survival of endometriosis