IL-33 Exacerbates Endometriotic Lesions via Polarizing Peritoneal Macrophages to M2 Subtype

Ono, Yuichi; Yokosuka, Osamu; Hiraoka, Takehiro; Akiyama, Ikumi; Sato, Erina; Ito, Masami; Kobayashi, Mutsumi; Nakashima, Akitoshi; Wada, Shinichiro; Onda, Takashi; Unno, Nobuya; Osuga, Yutaka

doi:10.1007/s43032-019-00090-9

Cited by 24 publications

(22 citation statements)

References 13 publications

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“…Th2 cells, along with M2 macrophages, eosinophils, basophils, and ILC2s, promote the type 2 immunity-induced fibrogenesis ( 16 ). This seems to occur exactly in endometriosis ( 62 , 99 ).…”

Section: Discussionmentioning

confidence: 86%

“…Through activation of DCs, TSLP can promote Th2 cell differentiation and propagate a type 2 immune response ( 16 ). Similarly, IL-33, which is in high concentration in endometriosis ( 60 , 61 , 63 , 99 ), can also induce a Th2 response on mast cells and Th2 cells ( 16 ). Th2 cell-derived IL-4 and IL-13 can alternatively activate macrophages ( 100 ) and suppress Th1 cells, resulting in increased Th2 cytokine production.…”

Section: Discussionmentioning

confidence: 99%

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Platelets and Regulatory T Cells May Induce a Type 2 Immunity That Is Conducive to the Progression and Fibrogenesis of Endometriosis

2020

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Endometriosis is a hormonal disease, as well as a chronic inflammatory disease. While various immune cells are documented to be involved in endometriosis, there is a wanton lack of a bigger picture on how these cells are coordinated to work concertedly. Since endometriotic lesions experience cyclical bleeding, they are fundamentally wounds that undergo repeated tissue injury and repair (ReTIAR). In this study, we attempted to characterize the role of platelets and regulatory T cells (Tregs) in modulating the lesional immune microenvironment and its subsequent effects on lesional progression and fibrogenesis. Through two mouse experiments, we show that, by disrupting predominantly a type 2 immune response in lesional microenvironment, both platelets and Tregs depletion decelerated lesional progression and fibrogenesis, likely through the suppression of the TGF-β1/Smad3 and PDGFR-β/PI3K/Akt signaling pathways. In particular, platelet depletion resulted in significantly reduced lesional expression of thymic stromal lymphopoietin (TSLP), leading to reduced aggregation of macrophages and alternatively activated (M2) macrophages, and of Tregs, T helper 2 (Th2) and Th17 cells but increased aggregation of Th1 cells, in lesions, which, in turn, yields retarded fibrogenesis. Similarly, Tregs depletion resulted in suppression of platelet aggregation, and reduced aggregation of M2 macrophages, Th2 and Th17 cells but increased aggregation of Th1 cells, in lesions. Thus, both platelet and Tregs depletion decelerated lesional progression and fibrogenesis by disrupting predominantly a type 2 immunity in lesional microenvironment. Taken together, this suggests that both platelets and Tregs may induce a type 2 immunity in lesional microenvironment that is conducive to lesional progression and fibrogenesis.

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“…Th2 cells, along with M2 macrophages, eosinophils, basophils, and ILC2s, promote the type 2 immunity-induced fibrogenesis ( 16 ). This seems to occur exactly in endometriosis ( 62 , 99 ).…”

Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Platelets and Regulatory T Cells May Induce a Type 2 Immunity That Is Conducive to the Progression and Fibrogenesis of Endometriosis

2020

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“…Our recent findings also show that HMGB1 levels are higher in non-immune cells and APCs obtained from endometrial cysts than those obtained from non-endometrial cysts (manuscript in preparation). A recent report suggested IL-33 is found in cystic fluid of ovarian tumors and is linked to the pathogenesis of endometriosis and infertility [126]. These findings indicate that the increased level of alermin releasing in pre-pregnancy might be the risk of infertility and recurrent pregnancy loss.…”

Section: Miscarriage and Infertilitymentioning

confidence: 81%

“…This indicates that the anti-inflammatory milieu enables ectopic endometrial lesions to survive in the pelvic cavity. IL-33, a known alarmin and a number of the IL-1 family that induces cytokines of the Th2 subtype, was expressed on endometriosis lesions [126,144].…”

Section: Endometriosismentioning

confidence: 99%

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Harmful and beneficial effects of inflammatory response on reproduction: sterile and pathogen-associated inflammation

Negishi

Shima

Takeshita

et al. 2020

Immunological Medicine

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In reproduction, inflammatory processes play important roles in the development of many pregnancy complications such as preterm labor/birth, recurrent pregnancy loss, recurrent implantation failure, and preeclampsia. Inflammation can be initiated by both microbial and non-microbial causes. Bacterial infection in the feto-maternal interface and uterus can provoke preterm labor/birth, miscarriage, and chronic endometritis. By contrast, inflammation without infection, or 'sterile inflammation,' can also lead to many kinds of complications, such as preterm labor/birth, miscarriage, or preeclampsia. Aberrant inflammation is facilitated by immune cells such as macrophages, dendritic cells, natural killer cells, and invariant natural killer T cells. In addition, cytokines, chemokines, and several kinds of inflammatory mediators are involved. On the other hand, appropriate inflammation is required for a successful offspring during the progression of the entire pregnancy. Herein, we discuss the relation between pregnancy and inflammation with immunological alterations. Understanding the role of inflammation in complications during pregnancy may establish new perspectives of the progress of normal pregnancy as well as treatments during pregnancy complications.

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Identifying Immune Cell Infiltration and Hub Genes Related to M2 Macrophages in Endometriosis by Bioinformatics Analysis

Zhu

Jin

et al. 2023

Reprod. Sci.

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IL-33 Exacerbates Endometriotic Lesions via Polarizing Peritoneal Macrophages to M2 Subtype

Cited by 24 publications

References 13 publications

Platelets and Regulatory T Cells May Induce a Type 2 Immunity That Is Conducive to the Progression and Fibrogenesis of Endometriosis

Platelets and Regulatory T Cells May Induce a Type 2 Immunity That Is Conducive to the Progression and Fibrogenesis of Endometriosis

Harmful and beneficial effects of inflammatory response on reproduction: sterile and pathogen-associated inflammation

Identifying Immune Cell Infiltration and Hub Genes Related to M2 Macrophages in Endometriosis by Bioinformatics Analysis

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