TLRs, macrophages, and NK cells: Our understandings of their functions in uterus and ovary

Yang, Ziyan; Kong, Beihua; Mosser, David M.; Zhang, Xia

doi:10.1016/j.intimp.2011.04.024

Cited by 61 publications

(53 citation statements)

References 159 publications

(304 reference statements)

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“…1,2 During the inflammatory response, tissue Mws are expected to sequentially develop into three different subpopulations: type-1 (Mw-1), type-2 (Mw-2) and regulatory (Reg-Mws). [3][4][5][6] During the initiation phase of inflammation, the pro-inflammatory Mw-1 subtype is generated in response to two signals (i.e., Interferon gamma (IFN-c) and tumor-necrosis factor alpha (TNF-a)) or a Toll-like receptor (TLR) ligand, such as lipopolysaccharide (LPS). During the resolution phase of inflammation, the presence of the type-2 cytokines interleukin 4 (IL-4) and IL-13 leads to the generation of anti-inflammatory Mw-2, which are associated with the coordination of tissue repair.…”

Section: Introductionmentioning

confidence: 99%

“…The third subtype (i.e., Reg-Mws) is fundamentally different from Mw-1 and Mw-2, and the generation of this subtype requires two signals. [3][4][5][6] The first signal may include IL-10, prostaglandins, immune complexes, adenine nucleotides, glucocorticoids and apoptotic cells, and the second signal is TLR activation. RegMws overproduce IL-10 but not IL-12 and exhibit potent immunosuppressive activity for modulating the acute inflammatory response and limiting tissue damage.…”

Section: Introductionmentioning

confidence: 99%

“…RegMws overproduce IL-10 but not IL-12 and exhibit potent immunosuppressive activity for modulating the acute inflammatory response and limiting tissue damage. [3][4][5][6] Tissue Mws constitute one of the most abundant populations of inflammatory cells in the uterus, and the numbers of these cells remain relatively constant in the decidua throughout gestation. 7,8 In normal pregnancies, the phenotype of uterine Mws is locally modified to acquire a type-2 phenotype, 9-11 which may contribute to trophoblast differentiation, support embryo implantation and supply growth factors to the placenta.…”

Section: Introductionmentioning

confidence: 99%

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The activating effect of IFN-γ on monocytes/macrophages is regulated by the LIF–trophoblast–IL-10 axis via Stat1 inhibition and Stat3 activation

et al. 2014

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Interferon gamma (IFN-c) and leukemia inhibitory factor (LIF) are key gestational factors that may differentially affect leukocyte function during gestation. Because IFN-c induces a pro-inflammatory phenotype in macrophages and because trophoblast cells are principal targets of LIF in the placenta, we investigated whether and how soluble factors from trophoblast cells regulate the effects of IFN-c on macrophage activation. IFN-c reduces macrophage motility, but enhances Stat1 activation, pro-inflammatory gene expression and cytotoxic functions. Soluble factors from villous cytotrophoblasts (vCT1LIF cells) and BeWo cells (BW/ST1LIF cells) that were differentiated in the presence of LIF inhibit macrophage Stat1 activation but inversely sustain Stat3 activation in response to IFN-c. vCT1LIF cells produce soluble factors that induce Stat3 activation; this effect is partially abrogated in the presence of neutralizing anti-interleukin 10 (IL-10) antibodies. Moreover, soluble factors from BW/ST1LIF cells reduce cell proliferation but enhance the migratory responses of monocytes. In addition, these factors reverse the inhibitory effect of IFN-c on monocyte/macrophage motility. BW/ST1LIF cells also generate IFN-c-activated macrophages with enhanced IL-10 expression, but reduced tumor-necrosis factor alpha (TNF-a), CD14 and CD40 expression as well as impaired cytotoxic function. Additional assays performed in the presence of neutralizing anti-IL-10 antibodies and exogenous IL-10 demonstrate that reduced macrophage cytotoxicity and proliferation, but increased cell motility result from the ability of trophoblast IL-10 to sustain Stat3 activation and suppress IFN-c-induced Stat1 activation. These in vitro studies are the first to describe the regulatory role of the LIF-trophoblast-IL-10 axis in the process of macrophage activation in response to pro-inflammatory cytokines.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The activating effect of IFN-γ on monocytes/macrophages is regulated by the LIF–trophoblast–IL-10 axis via Stat1 inhibition and Stat3 activation

et al. 2014

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“…For example, green fluorescent protein lineage tracing using the collagen 1 ␣ 1 promoter found this to be a rather rare phenomenon during renal fibrogenesis upon ureteral obstruction in mice [99] . The chemokine receptor CCR1 seems to be essential for the recruitment and activation of profibrotic macrophages and fibrocytes because a lack of CCR1 or CCR1 antagonism prevents progressive tissue fibrosis in many disease states and organs [100][101][102][103][104][105][106][107][108][109] . The first reports to document macrophages contributing to dermal fibrosis date back to the mid-seventies [110] .…”

Section: Tissue Environments Dominated By Parenchymal Atrophy and Gromentioning

confidence: 99%

Tissue Microenvironments Define and Get Reinforced by Macrophage Phenotypes in Homeostasis or during Inflammation, Repair and Fibrosis

Weidenbusch¹,

Anders²

2012

J Innate Immun

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Current macrophage phenotype classifications are based on distinct in vitro culture conditions that do not adequately mirror complex tissue environments. In vivo monocyte progenitors populate all tissues for immune surveillance which supports the maintenance of homeostasis as well as regaining homeostasis after injury. Here we propose to classify macrophage phenotypes according to prototypical tissue environments, e.g. as they occur during homeostasis as well as during the different phases of (dermal) wound healing. In tissue necrosis and/or infection, damage- and/or pathogen-associated molecular patterns induce proinflammatory macrophages by Toll-like receptors or inflammasomes. Such classically activated macrophages contribute to further tissue inflammation and damage. Apoptotic cells and an- tiinflammatory cytokines dominate in postinflammatory tissues which induce macrophages to produce more anti-inflammatory mediators. Similarly, tumor-associated macrophages also confer immunosuppression in tumor stroma. Insufficient parenchymal healing despite abundant growth factors pushes macrophages to gain a profibrotic phenotype and promote fibrocyte recruitment which both enforce tissue scarring. Ischemic scars are largely devoid of cytokines and growth factors so that fibrolytic macrophages that predominantly secrete proteases digest the excess extracellular matrix. Together, macrophages stabilize their surrounding tissue microenvironments by adapting different phenotypes as feed-forward mechanisms to maintain tissue homeostasis or regain it following injury. Furthermore, macrophage heterogeneity in healthy or injured tissues mirrors spatial and temporal differences in microenvironments during the various stages of tissue injury and repair.

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“…An interesting article by Dr. Zhang and colleagues [7] discusses the role of TLRs in macrophages and natural killer (NK) cells in female reproductive health. Macrophages and NK cells participate in a wide range of patho-physiological processes in the female reproductive organs and adapt their phenotype to the local micro-environment.…”

mentioning

confidence: 99%

Toll-like receptors and diseases

Iribarren¹,

Wang²

2011

International Immunopharmacology

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TLRs, macrophages, and NK cells: Our understandings of their functions in uterus and ovary

Cited by 61 publications

References 159 publications

The activating effect of IFN-γ on monocytes/macrophages is regulated by the LIF–trophoblast–IL-10 axis via Stat1 inhibition and Stat3 activation

The activating effect of IFN-γ on monocytes/macrophages is regulated by the LIF–trophoblast–IL-10 axis via Stat1 inhibition and Stat3 activation

Tissue Microenvironments Define and Get Reinforced by Macrophage Phenotypes in Homeostasis or during Inflammation, Repair and Fibrosis

Toll-like receptors and diseases

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