CCL22 controls immunity by promoting regulatory T cell communication with dendritic cells in lymph nodes

Rapp, Moritz; Wintergerst, Maximilian W. M.; Kunz, Wolfgang G.; Vetter, Viola; Knott, Max; Lisowski, Dominik; Haubner, Sascha; Moder, Stefan; Thaler, Raffael; Eiber, Stephan; Meyer, Bastian; Röhrle, Natascha; Piseddu, Ignazio; Grassmann, Simon; Layritz, Patrick; Kühnemuth, Benjamin; Stutte, Susanne; Bourquin, Carole; Andrian, Ulrich H. von; Endres, Stefan; Anz, David

doi:10.1084/jem.20170277

Cited by 175 publications

(147 citation statements)

References 59 publications

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“…CCL22 is induced by the Th2 cytokines IL-4 and IL-13 [8]. CCL22 is also identified as a T-regulatory-associated chemokine [23], by promoting regulatory T cell communication with dendritic cells in lymph nodes [24].The present study showed an elevated level of CCL22 in patients with hyperprolactinemia compared with healthy controls. Hyperprolactinemia patients also showed a higher level of the B cell attracting chemokine CXCL13, and prolactin levels correlated positively with both CCL22 and CXCL13.…”

Section: Discussionsupporting

confidence: 55%

Immunomodulating Effects Depend on Prolactin Levels in Patients with Hyperprolactinemia

et al. 2020

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Prolactin is known to have immune modulatory effects acting through the prolactin receptor, which is present on a variety of immune cells. Certain chemokines contribute to form the type of T helper (Th) preponderance in the immune response. The objective of this work was to assess if hyperprolactinemia not related to pregnancy is associated with changes in circulating levels of chemokines and other immunological markers. In this cross sectional study, 35 patients with hyperprolactinemia (5 men), and 102 healthy blood donors (19 men) were included. Serum levels of Th1- Th2- and Th17-associated chemokines, C-reactive protein, immunoglobulins, and the B cell attracting chemokine CXCL13 were assessed. The hyperprolactinemic group had significantly higher levels of Th2 associated CCL22 (p=0.022), Th17 associated CXCL1 (p=0.001), B cell attracting CXCL13 (p=0.003), and C-reactive protein (p<0.001) compared to controls, and these proteins were also positively correlated with prolactin levels. While differences in CCL22, CXCL1, CXCL13, and C-reactive protein were present in patients with low or moderate hyperprolactinemia, no differences were observed at high (>3600 mU/l) prolactin levels. To evaluate a possible dose-associated response to prolactin, an in vitro model was used, showing prolactin-induced increase in T-helper cell activation at moderate levels, while activation decreased at higher levels. Hyperprolactinemia seems to have several immunomodulatory effects and was associated with increased levels of chemokines associated with Th2 and Th17 responses and B cell attraction. However, patients with greatly increased prolactin had normal levels of chemokines, and in vitro, high levels of prolactin decreased T-helper cell activation.

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Section: Discussionsupporting

confidence: 55%

Immunomodulating Effects Depend on Prolactin Levels in Patients with Hyperprolactinemia

et al. 2020

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“…More importantly, human LN DCs are understudied and even though we were unable to decipher more than one LN DC cluster, there is a wealth of genetic information provided in this datum. For instance, CCL17 and CCL22 expression is restricted to DC populations in lung and LNs, and not expressed on human blood DCs 65,66,67,68 . This is also true in mice, where these chemokines distinguish DCs from other immune cell types and are important for T cell recruitment and interactions.…”

Section: Discussionmentioning

confidence: 99%

Human and mouse transcriptome profiling identifies cross-species homology in pulmonary and lymph node mononuclear phagocytes

Leach

Gibbings

Tewari

et al. 2020

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The mononuclear phagocyte (MP) system consists of macrophages, monocytes, and dendritic cells (DCs). MP subtypes play distinct functional roles in steady-state and inflammatory conditions. Though murine MPs are well-characterized, their human homologs remain poorly understood. To address this gap, we created a gene expression compendium across 15-distinct human and 9-distinct murine MPs from lung, LN, blood, and spleen. This study identified corresponding human-mouse MP subtypes and determined marker genes shared or not between species counterparts. Unexpectedly, at the gene expression level, only 13-23% of the top 1000 marker genes overlapped in corresponding human-mouse MP counterparts, indicating a need for caution when translating mouse studies to human gene targets and functions. Lastly, CD88 was useful in both species to distinguish macrophage/monocytes from DCs. Our cross-species expression compendium serves as a resource for future translational studies to investigate beforehand whether pursuing specific MP subtypes, or gene will prove fruitful. 12 . Murine pulmonary MPs consist of alveolar macrophages (AMs), tissue trafficking monocytes, dendritic cell (DCs) subtypes 12, 13 , and three interstitial macrophages (IMs):two IMs, IM1-(CD206 hi MHCII + ) and IM2-(CD206 hi MHCII lo ), display classical macrophage characteristics, whereas the third IM, IM3-(CD206 lo MHCII + ), although displaying macrophage properties, has a higher rate of turnover and expresses pro-inflammatory, monocytic and DC genes 7 . Very little is known about IMs, in humans how to identify them, and in both species, humans and mice, how they functionally contribute to homeostasis, inflammation, or disease. Most notably, with the exception of AMs, all other MP subtypes described above reside in multiple organs 14,15,16,17 .Functionally, circulating monocytes traditionally have been viewed as precursors to tissue-resident macrophages. However, now we know that monocytes continuously traffic through non-lymphoid and lymphoid tissue, where they survey the environment, and unless there is a macrophage niche to fill, steady-state monocytes do not differentiate into self-renewing, tissue resident macrophages 18,19 . During inflammation, monocytes can differentiate into inflammatory and resolving macrophages, which display distinct properties from resident macrophages 10,20,21,22 . In lymphoid tissue, even though LN monocytes are highly present, their role in adaptive immunity is less defined than DCs 19, .DCs are potent antigen-presenting cells that link innate and adaptive immunity. In the periphery, DCs can acquire pathogens, traffic through lymphatic vessels to draining LNs, and present exogenous antigens to cognate T cells, precipitating adaptive immunity 11,24,25,26,27 . In mice, there are two main DC types referred to as Batf3 + DC1 and Irf4 +

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“…Expression level augmentation has notably been observed for proinflammatory cytokines such as CCL11 and CCL22 (Fig. 8) which are different chemokines needed to recruit cells populations from immune system [45]. IFNγ and TNFα also showed an increase in expression level, which are well known proinflammatory cytokines.…”

Section: Common Toxicity Mechanism Of Mwcntmentioning

confidence: 91%

“…Venn diagrams based on transcriptomic analysis results showing the number of common genes dysregulated[45] after NR8383 cells exposure to three MWCNT and the number of genes specific to each exposure at fold change, FC ≥ 1.5 (70 for NM403, 38 for NRCWE-042 and 2876 for NRCWE-049). The main biological process (Gene ontology) common a specific for MWCNT studied were presented (DAVID analysis) Nahle et al J Nanobiotechnol (2020)18:36 …”

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confidence: 99%

Genes expression profiling of alveolar macrophages exposed to non-functionalized, anionic and cationic multi-walled carbon nanotubes shows three different mechanisms of toxicity

et al. 2020

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Functionalized multi-walled carbon nanotubes (MWCNT) have become the focus of increased research interest, particularly in their application as tools in different areas, such as the biomedical field. Despite the benefits associated with functionalization of MWCNT, particularly in overcoming issues relating to solubility, several studies have demonstrated that these functionalized nanoparticles display different toxicity profiles. For this study, we aim to compare NR8383 cells responses to three well-characterized MWCNT with varying functional groups. This study employed cytotoxicity assays, transcriptomics and proteomics to assess their toxicity using NR8383 rat alveolar macrophages as an in vitro model. The study findings indicated that all MWCNT altered ribosomal protein translation, cytoskeleton arrangement and induced pro-inflammatory response. Only functionalized MWCNT alter mTOR signaling pathway in conjunction with increased Lamtor gene expression. Furthermore, the type of functionalization was also important, with cationic MWCNT activating the transcription factor EB and inducing autophagy while the anionic MWCNT altering eukaryotic translation initiation factor 4 (EIF4) and phosphoprotein 70 ribosomal protein S6 kinase (p70S6K) signaling pathway as well as upregulation Tlr2 gene expression. This study proposes that MWCNT toxicity mechanisms are functionalization dependent and provides evidence that inflammatory response is a key event of carbon nanotubes toxicity.© The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article' s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article'

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CCL22 controls immunity by promoting regulatory T cell communication with dendritic cells in lymph nodes

Cited by 175 publications

References 59 publications

Immunomodulating Effects Depend on Prolactin Levels in Patients with Hyperprolactinemia

Immunomodulating Effects Depend on Prolactin Levels in Patients with Hyperprolactinemia

Human and mouse transcriptome profiling identifies cross-species homology in pulmonary and lymph node mononuclear phagocytes

Genes expression profiling of alveolar macrophages exposed to non-functionalized, anionic and cationic multi-walled carbon nanotubes shows three different mechanisms of toxicity

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