Regulation of Interleukin-12 Production in Antigen-Presenting Cells

Zheng, Hua; Y, Ban; Wei, Fang; Ma, Xiaojing

doi:10.1007/978-94-024-0921-5_6

Cited by 47 publications

(36 citation statements)

References 109 publications

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“…IL-12p70 is produced mostly by antigen-presenting cells such as macrophages and dendritic cells. It exerts an immune-stimulatory role on NK cells and promotes differentiation of naive CD4+ T lymphocytes into Th1 cells that produce IFN-γ and TNF-α as part of the innate and adaptive immune responses against endogenous damage [ 73 ]. Importantly, IL-12p70 was increased at menopause [ 11 ] and the level of p40 subunit was positively associated with parity [ 8 ].…”

Section: Discussionmentioning

confidence: 99%

Parity History Determines a Systemic Inflammatory Response to Spread of Ovarian Cancer in Naturally Aged Mice

Urzúa

Chacón

Lizama³

et al. 2017

Aging and disease

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Aging intersects with reproductive senescence in women by promoting a systemic low-grade chronic inflammation that predisposes women to several diseases including ovarian cancer (OC). OC risk at menopause is significantly modified by parity records during prior fertile life. To date, the combined effects of age and parity on the systemic inflammation markers that are particularly relevant to OC initiation and progression at menopause remain largely unknown. Herein, we profiled a panel of circulating cytokines in multiparous versus virgin C57BL/6 female mice at peri-estropausal age and investigated how cytokine levels were modulated by intraperitoneal tumor induction in a syngeneic immunocompetent OC mouse model. Serum FSH, LH and TSH levels increased with age in both groups while prolactin (PRL) was lower in multiparous respect to virgin mice, a finding previously observed in parous women. Serum CCL2, IL-10, IL-5, IL-4, TNF-α, IL1-β and IL-12p70 levels increased with age irrespective of parity status, but were specifically reduced following OC tumor induction only in multiparous mice. Animals developed hemorrhagic ascites and tumor implants in the omental fat band and other intraperitoneal organs by 12 weeks after induction, with multiparous mice showing a significantly extended survival. We conclude that previous parity history counteracts aging-associated systemic inflammation possibly by reducing the immunosuppression that typically allows tumor spread. Results suggest a partial impairment of the M2 shift in tumor-associated macrophages as well as decreased stimulation of regulatory B-cells in aged mice. This long term, tumor-concurrent effect of parity on inflammation markers at menopause would be a contributing factor leading to decreased OC risk.

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Section: Discussionmentioning

confidence: 99%

Parity History Determines a Systemic Inflammatory Response to Spread of Ovarian Cancer in Naturally Aged Mice

Urzúa

Chacón

Lizama³

et al. 2017

Aging and disease

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“…IL12 is a cytokine produced by APC-when they are activated by exposure to antigens [40,44]. In terms of antigen processing, the differences between the treatment arms is the source of the APCs: endogenous in situ APC in the case of TCV, and ex vivo antigen loaded DC in the case of DCV.…”

Section: T-helper Cytotoxic Pathways (Th1 Th17 Pathways)mentioning

confidence: 99%

“…These cells can augment immunosuppressive or immune enhancing effects depending on the microenvironment and local cytokines [34][35][36][37]. At the nexus of innate and adaptive immunity, are antigen-presenting cells, especially dendritic cells [38], that are characterized by secretion of IL12 when activated [39][40][41][42][43][44]. As part of maintaining homeostasis of the immune system, there are also a number of cytokines including such as PD-1 [45,46], IL10 [47][48][49], transforming growth factor beta (TGFβ) [50][51][52], beta-2-microglobulin (B2M) [53,54], and Fas (CD95) [55], that are associated with suppressed immune responses.…”

mentioning

confidence: 99%

Cytokine network analysis of immune responses before and after autologous dendritic cell and tumor cell vaccine immunotherapies in a randomized trial

Nistor¹,

Dillman²

2020

J Transl Med

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Background: In a randomized phase II trial conducted in patients with metastatic melanoma, patient-specific autologous dendritic cell vaccines (DCV) were associated with longer survival than autologous tumor cell vaccines (TCV). Both vaccines presented antigens from cell-renewing autologous tumor cells. The current analysis was performed to better understand the immune responses induced by these vaccines, and their association with survival. Methods: 110 proteomic markers were measured at a week-0 baseline, 1 week before the first of 3 weekly vaccine injections, and at week-4, 1 week after the third injection. Data was presented as a deviation from normal controls. A two-component principal component (PC) statistical analysis and discriminant analysis were performed on this data set for all patients and for each treatment cohort. Results: At baseline PC-1 contained 64.4% of the variance and included the majority of cytokines associated with Th1 and Th2 responses, which positively correlated with beta-2-microglobulin (B2M), programmed death protein-1 (PD-1) and transforming growth factor beta (TGFβ1). Results were similar at baseline for both treatment cohorts. After three injections, DCV-treated patients showed correlative grouping among Th1/Th17 cytokines on PC-1, with an inverse correlation with B2M, FAS, and IL-18, and correlations among immunoglobulins in PC-2. TCV-treated patients showed a positive correlation on PC-1 among most of the cytokines and tumor markers B2M and FAS receptor. There were also correlative changes of IL12p40 with both Th1 and Th2 cytokines and TGFβ1. Discriminant analysis provided additional evidence that DCV was associated with innate, Th1/Th17, and Th2 responses while TCV was only associated with innate and Th2 responses. Conclusions: These analyses confirm that DCV induced a different immune response than that induced by TCV, and these immune responses were associated with improved survival. Trial registration Clinical trials.gov NCT004936930 retrospectively registered

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“…1F). The overall M1 to M2 ratio showed a decreased in M1/M2 percentages ( IL-12 is produced by activated antigen-presenting cells (dendritic cells, macrophages) [18]. It promotes the development of Th1 responses and is a powerful inducer of IFNγ production by T and NK cells [19].…”

Section: Elevated Frequencies Of Programmed Death Ligand 2 (Pdl2) In mentioning

confidence: 99%

Interleukin-4 retards liver fibrosis in BALB/c mice model of carbon tetra-chloride (CCl4)-associated with decreased CD80 and interleukin-12 expressions

Amer

Hattab

Rahal

2019

Preprint

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Background: BALB/c mice showed easily induced Th2-type responses in several infection models. Certain macrophage phenotypes contribute to liver fibrosis. We characterized changes in macrophages phenotype (M1/M2) during fibrogenesis in liver fibrosis mice model. Methods: Carbon-tetrachloride (CCl 4 ) hepatic-fibrosis was induced in BALB/c mice. Liver macrophages isolated were identified for M1 and M2 by CD80/iNOS and CD273 (programmed death ligand 2 (PDL2)/CD206, respectively. IL-4 were induced i.p along week-2 to week-4 of CCl 4 . Liver proteins were assessed for aSMA expressions, histology and ALT levels. Results: CCl 4 -induced hepatic-fibrosis showed increased CD273 (from 20.1%± 3.1in naïve mice to 27.8%±3.2 in fibrotic mice; P=0.01) while gradual decrease in CD80 (from 12%±6.2 in naïve mice to 1.97%±0.4 in fibrotic mice; P<0.02). The overall data showed decreased M1/M2 ratio. M2-macrophages showed inhibited expressions of IFN-g, IL-12 and vitamin-D-receptor (VDR) while high TGF-b levels. ALT, H&E staining intensities and aSMA showed gradually increased along fibrosis while metabolic markers of serum insulin, vitamin D and VDR decreased. IL-4 inductions while inhibited fibrosis it elevated metabolic markers. Conclusions: M2-macrophages express less IFN-g and IL-12, which might indicate inability differentiation of naive T cells into Th1 cells. IL-4 has an anti-fibrotic effects through antagonize M2-macrophages of TGF-b and ameliorating insulin, vitamin D, VDR and consequently attenuated liver-fibrosis.

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Regulation of Interleukin-12 Production in Antigen-Presenting Cells

Cited by 47 publications

References 109 publications

Parity History Determines a Systemic Inflammatory Response to Spread of Ovarian Cancer in Naturally Aged Mice

Parity History Determines a Systemic Inflammatory Response to Spread of Ovarian Cancer in Naturally Aged Mice

Cytokine network analysis of immune responses before and after autologous dendritic cell and tumor cell vaccine immunotherapies in a randomized trial

Interleukin-4 retards liver fibrosis in BALB/c mice model of carbon tetra-chloride (CCl4)-associated with decreased CD80 and interleukin-12 expressions

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