Mechanisms of allergy and clinical immunologyEnhanced production of CCL18 by tolerogenic dendritic cells is associated with inhibition of allergic airway reactivity
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Blood samples
Heparinized blood was obtained from atopic donors with allergic rhinoconjunctivitis and/or asthma to grass or birch pollen or house dust mite. Specific sensitization was documented by positive skin prick test responses and detection of allergen-specific IgE in sera (CAP class ≥2 and CAP class ≥5 for studies in humanized mice, as measured with the ImmunoCAP specific IgE blood test; Phadia AB, Uppsala, Sweden). This study was approved by the local ethics committee. Informed consent was obtained
Transcriptional profile revealed that CCL18 is upregulated in cocultures of CD4+ T cells with allergen-pulsed, tolerogenic, IL-10–treated DCs compared with regular allergen-pulsed DCs
CD4+ T cells from donors with grass pollen allergy were cocultured with allergen-pulsed DCs or IL-10–treated DCs. After 24 hours, the RNA was extracted for microarray analysis by using Affymetrix technology. Table I shows all the genes transcribed at an enhanced or reduced rate after evaluation of the results from 3 different donors by using Array Assist software (P < .05). Although 20 of 21 genes were upregulated in cocultures of CD4+ T cells and allergen-pulsed DCs compared with IL-10–treated
Discussion
In the present study we have investigated the gene expression profile of CD4+ T cells from allergic donors cocultured with autologous allergen-pulsed DCs or tolerogenic IL-10–treated DCs. We found that the gene encoding the chemokine CCL18 was the only gene significantly upregulated in cocultures of CD4+ T cells and IL-10–treated DCs. In functional analysis we have shown that enhanced CCL18 production is associated with recruitment of Treg cells and inhibition of TH2 responses in vitro. Most
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The immunosuppressive and pro-tumor functions of CCL18 at the tumor microenvironment
2021, Cytokine and Growth Factor ReviewsCitation Excerpt :This further boosts the promotion of a Th2 and Treg response [41,42]. As seen in physiologic conditions, tolerogenic DCs are able to produce CCL18 [11,43] and may contribute to the high levels of this chemokine within tumors. Adding to these cellular sources, cancer cells themselves are also described to produce CCL18, as demonstrated in ovarian [44] and gastric [45] cancers, in pancreatic ductal adenocarcinoma [37] and in oral squamous cell carcinoma.
Lupine protein hydrolysates decrease the inflammatory response and improve the oxidative status in human peripheral lymphocytes
2019, Food Research InternationalCitation Excerpt :For example, inhibitory effects of recombinant β1-, β3-, and β6-conglutin proteins from Lupinus angustifolius have been shown on IL-1β and inducible nitric oxide synthase (iNOS) levels in in vitro cultured PBMCs from type 2 diabetes patients (Lima-Cabello et al., 2017). We have also previously described the inhibitory effects of LPHs on TNF production in macrophages derived from THP-1 human monocytic cell line and their upregulation of the mRNA expression of CCL18 (Millan-Linares, Bermudez, et al., 2014), a Th2-associated chemokine (Bellinghausen et al., 2012). Our present results support the anti-inflammatory effects of LPHs, which occur through not only a decrease in TNF levels but also the inhibition of additional Th1 cytokines, such as IL-2, IL-12, and IFNγ.
Wheat amylase-trypsin inhibitors exacerbate intestinal and airway allergic immune responses in humanized mice
2019, Journal of Allergy and Clinical ImmunologyCitation Excerpt :Finally, numbers of murine neutrophils in the bronchoalveolar lavage fluid of PBMC plus allergen–treated mice were slightly but not significantly increased in mice receiving the ATI-containing diet (Fig 4, D). As previously published, murine eosinophils and human TH2 cytokines were not detectable in the bronchoalveolar lavage of this PBMC-engrafted humanized mouse model.13,16 After measurement of allergen-induced gut and lung inflammation, human CD4+ T cells recovered from mice spleens were restimulated with autologous DCs that were pulsed with the same allergen by which the mice were challenged.
Analysis of allergic immune responses in humanized mice
2016, Cellular ImmunologyCitation Excerpt :Now, we could confirm these results in our humanized mouse model, where administration of CCL18 significantly prevented airway reactivity, while another Th2-attracting chemokine, CCL17, did not. Inhibition of lung inflammation further demonstrated by reduced mucus production and goblet cell hyperplasia was associated with a slight increase of GARP (Glycoprotein A Repetitions Predominant)-expressing Treg, a marker which had been described to be up-regulated on activated Treg and to play an important role on their regulatory function [70,73,74]. More recently, we were able to show that GARP-expressing activated Treg or administration of rGARP itself also inhibited human total and allergen-specific IgE and subsequent allergen-driven IgE-dependent gut inflammation, the latter by increasing Treg numbers [75].
Activated glycoprotein A repetitions predominant (GARP)-expressing regulatory T cells inhibit allergen-induced intestinal inflammation in humanized mice
2015, Journal of Allergy and Clinical ImmunologyAdvances in mechanisms of allergy and clinical immunology in 2012
2013, Journal of Allergy and Clinical ImmunologyCitation Excerpt :Thus Treg cells act upstream of DCs in this model of low-zone tolerance to limit sensitization and skin pathology. Finally, Bellinghausen et al40 demonstrated that treatment of DCs with IL-10 before coculture with naive T cells downregulated TH2 cytokine generation and OX40 on T cells, with an unexpected marked induction of the DC-derived chemokine CCL18. The addition of CCL18 to the cocultures reproduced the protolerance effect of the DCs, even without IL-10 priming.
Supported by Deutsche Forschungsgemeinschaft (DFG) SFB 548 TP A4 and BE 4504/2-1 grant.
Disclosure of potential conflict of interest: I. Bellinghausen has received one or more grants from and has received support for travel from the DFG (grant BE 4504/2-1). J. Saloga has received one or more grants from the German Research Foundation, has received one or more grants from or has one or more grants pending with the pharmaceutical industry, and has received one or more payments for lecturing from or is on the speakers’ bureau for the pharmaceutical industry. The rest of the authors declare that they have no relevant conflicts of interest.