scholarly journals Migratory CD103+ dendritic cells suppress helminth-driven type 2 immunity through constitutive expression of IL-12

2015 ◽  
Vol 213 (1) ◽  
pp. 35-51 ◽  
Author(s):  
Bart Everts ◽  
Roxane Tussiwand ◽  
Leentje Dreesen ◽  
Keke C. Fairfax ◽  
Stanley Ching-Cheng Huang ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Constitutive Expression ◽  
Helminth Parasites ◽  
Th2 Response ◽  
Heligmosomoides Polygyrus ◽  
Th2 Cell ◽  
Type 2 Immunity ◽  
Necessary And Sufficient

CD8α+ and CD103+ dendritic cells (DCs) play a central role in the development of type 1 immune responses. However, their role in type 2 immunity remains unclear. We examined this issue using Batf3−/− mice, in which both of these DC subsets are missing. We found that Th2 cell responses, and related events such as eosinophilia, alternative macrophage activation, and immunoglobulin class switching to IgG1, were enhanced in Batf3−/− mice responding to helminth parasites. This had beneficial or detrimental consequences depending on the context. For example, Batf3 deficiency converted a normally chronic intestinal infection with Heligmosomoides polygyrus into an infection that was rapidly controlled. However, liver fibrosis, an IL-13–mediated pathological consequence of wound healing in chronic schistosomiasis, was exacerbated in Batf3−/− mice infected with Schistosoma mansoni. Mechanistically, steady-state production of IL-12 by migratory CD103+ DCs, independent of signals from commensals or TLR-initiated events, was necessary and sufficient to exert the suppressive effects on Th2 response development. These findings identify a previously unrecognized role for migratory CD103+ DCs in antagonizing type 2 immune responses.

scholarly journals Metabolic Interdependency of Th2 Cell-Mediated Type 2 Immunity and the Tumor Microenvironment

2021 ◽  
Vol 12 ◽  
Author(s):  
Simon Schreiber ◽  
Christoph M. Hammers ◽  
Achim J. Kaasch ◽  
Burkhart Schraven ◽  
Anne Dudeck ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Microenvironment ◽  
Allergic Diseases ◽  
Building Blocks ◽  
Th2 Cells ◽  
Th Cells ◽  
Th2 Cell ◽  
Type 2 Immunity ◽  
Mediate Immunity

The function of T cells is critically dependent on their ability to generate metabolic building blocks to fulfil energy demands for proliferation and consecutive differentiation into various T helper (Th) cells. Th cells then have to adapt their metabolism to specific microenvironments within different organs during physiological and pathological immune responses. In this context, Th2 cells mediate immunity to parasites and are involved in the pathogenesis of allergic diseases including asthma, while CD8+ T cells and Th1 cells mediate immunity to viruses and tumors. Importantly, recent studies have investigated the metabolism of Th2 cells in more detail, while others have studied the influence of Th2 cell-mediated type 2 immunity on the tumor microenvironment (TME) and on tumor progression. We here review recent findings on the metabolism of Th2 cells and discuss how Th2 cells contribute to antitumor immunity. Combining the evidence from both types of studies, we provide here for the first time a perspective on how the energy metabolism of Th2 cells and the TME interact. Finally, we elaborate how a more detailed understanding of the unique metabolic interdependency between Th2 cells and the TME could reveal novel avenues for the development of immunotherapies in treating cancer.

scholarly journals ncRNAs in Type-2 Immunity

2020 ◽  
Vol 6 (1) ◽  
pp. 10 ◽  
Author(s):  
Riccardo Guidi ◽  
Christopher J. Wedeles ◽  
Mark S. Wilson
Keyword(s):  
Immune Responses ◽  
Immune Cell ◽  
Allergic Diseases ◽  
Parasitic Helminths ◽  
Medical Needs ◽  
Type 2 Immunity ◽  
Non Coding Rna ◽  
Immune Mediated ◽  
Immunological Diseases

Immunological diseases, including asthma, autoimmunity and immunodeficiencies, affect a growing percentage of the population with significant unmet medical needs. As we slowly untangle and better appreciate these complex genetic and environment-influenced diseases, new therapeutically targetable pathways are emerging. Non-coding RNA species, which regulate epigenetic, transcriptional and translational responses are critical regulators of immune cell development, differentiation and effector function, and may represent one such new class of therapeutic targets. In this review we focus on type-2 immune responses, orchestrated by TH2 cell-derived cytokines, IL-4, IL-5 and IL-13, which stimulate a variety of immune and tissue responses- commonly referred to as type-2 immunity. Evolved to protect us from parasitic helminths, type-2 immune responses are observed in individuals with allergic diseases, including Asthma, atopic dermatitis and food allergy. A growing number of studies have identified the involvement of various RNA species, including microRNAs (miRNA) and long non-coding (lncRNA), in type-2 immune responses and in both clinical and pre-clinical disease settings. We highlight these recent findings, identify gaps in our understanding and provide a perspective on how our current understanding can be harnessed for novel treat opportunities to treat type-2 immune-mediated diseases.

scholarly journals Friend virus limits adaptive cellular immune responses by imprinting a maturation-resistant and T helper type 2-biased immunophenotype in dendritic cells

PLoS ONE ◽  
2018 ◽  
Vol 13 (2) ◽  
pp. e0192541 ◽  
Author(s):  
Limei Shen ◽  
Stefan Tenzer ◽  
Moritz Hess ◽  
Ute Distler ◽  
Ingrid Tubbe ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Friend Virus ◽  
T Helper ◽  
Cellular Immune Responses ◽  
Cellular Immune ◽  
Helper Type

scholarly journals ADAM10 and Notch1 on murine dendritic cells control the development of type 2 immunity and IgE production

Allergy ◽  
2017 ◽  
Vol 73 (1) ◽  
pp. 125-136 ◽  
Author(s):  
S. R. Damle ◽  
R. K. Martin ◽  
C. L. Cockburn ◽  
J. C. Lownik ◽  
J. A. Carlyon ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Type 2 Immunity

scholarly journals A mechanism for the induction of type 2 immune responses by a protease allergen in the genital tract

2017 ◽  
Vol 114 (7) ◽  
pp. E1188-E1195 ◽  
Author(s):  
Ji Eun Oh ◽  
Dong Sun Oh ◽  
Hi Eun Jung ◽  
Heung Kyu Lee
Keyword(s):  
Immune Responses ◽  
Genital Tract ◽  
Primary Response ◽  
Lymphoid Cells ◽  
Genital Mucosa ◽  
Type 2 Immunity ◽  
Parasite Infections ◽  
Barrier Surface ◽  
External Stimuli

The genital mucosa is a barrier that is constantly exposed to a variety of pathogens, allergens, and external stimuli. Although both allergen exposure and parasite infections frequently occur in the genital area, the mechanism by which immune responses—particularly type 2 immunity—are induced has rarely been studied in the genital mucosa. Here, we demonstrate the induction of T helper type 2 (Th2) immunity in the genital mucosa in response to a model allergen, the protease papain. Intravaginal papain immunization induced type 2 immunity in a manner that was dependent on protease activity and the estrous phase of the mice. In addition, IL-33 was released from the vaginal epithelia after intravaginal papain immunization, leading to the activation of type 2 innate lymphoid cells (ILC2s). Moreover, the IL-33–MyD88 (myeloid differentiation primary response gene 88) signaling pathway was critical for the induction of type 2 immunity. We also found that Th2 differentiation in response to intravaginal papain treatment requires a specific dendritic cell (DC) subset that is controlled by interferon regulatory factor 4 (IRF4). These findings suggest that type 2 immunity is induced by a unique mechanism in the genital tract, which is an important, but often overlooked, barrier surface.

scholarly journals A helminth-derived suppressor of ST2 blocks allergic responses

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Francesco Vacca ◽  
Caroline Chauché ◽  
Abhishek Jamwal ◽  
Elizabeth C Hinchy ◽  
Graham Heieis ◽  
...  
Keyword(s):  
Immune Responses ◽  
Heligmosomoides Polygyrus ◽  
Human Pbmc ◽  
Complement Control Protein ◽  
High Affinity ◽  
Intestinal Nematode ◽  
Control Protein

The IL-33-ST2 pathway is an important initiator of type 2 immune responses. We previously characterised the HpARI protein secreted by the model intestinal nematode Heligmosomoides polygyrus, which binds and blocks IL-33. Here, we identify H. polygyrus Binds Alarmin Receptor and Inhibits (HpBARI) and HpBARI_Hom2, both of which consist of complement control protein (CCP) domains, similarly to the immunomodulatory HpARI and Hp-TGM proteins. HpBARI binds murine ST2, inhibiting cell surface detection of ST2, preventing IL-33-ST2 interactions, and inhibiting IL-33 responses in vitro and in an in vivo mouse model of asthma. In H. polygyrus infection, ST2 detection is abrogated in the peritoneal cavity and lung, consistent with systemic effects of HpBARI. HpBARI_Hom2 also binds human ST2 with high affinity, and effectively blocks human PBMC responses to IL-33. Thus, we show that H. polygyrus blocks the IL-33 pathway via both HpARI which blocks the cytokine, and also HpBARI which blocks the receptor.

scholarly journals Adenosine metabolized from extracellular ATP promotes type 2 immunity through triggering A2BAR signaling on intestinal epithelial cells

2021 ◽  
Author(s):  
Darine W. El-Naccache ◽  
Fei Chen ◽  
Mark Palma ◽  
Alexander Lemenze ◽  
Wenhui Wu ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Extracellular Atp ◽  
Primary Response ◽  
Intestinal Epithelial ◽  
Intestinal Immunity ◽  
Heligmosomoides Polygyrus ◽  
Intestinal Nematode ◽  
Nematode Parasites ◽  
Type 2 Immunity

AbstractMulticellular intestinal nematode parasites can cross the epithelial barrier potentially causing tissue damage and release of danger associated molecular patterns (DAMPs) that may promote type 2 responses and host protective immunity. We investigated whether adenosine specifically binding the A2B adenosine receptor (A2BAR) on epithelial cells played an important role in driving intestinal immunity. Specific blockade of epithelial cell A2BAR inhibited the host protective memory response to the enteric helminth, Heligmosomoides polygyrus bakeri, including disruption of granuloma development at the host:parasite interface during the transient tissue dwelling larval stage. Memory T cell development was blocked during the primary response and transcriptional analyses revealed profound impairment of A2BAR signaling in epithelial cells and reduced type 2 markers by 24 hours after inoculation. Extracellular ATP was visualized by 24 hours after inoculation and shown in CD39 deficient mice to be critical for the adenosine production mediating initiation of type 2 immunity.

scholarly journals Transcriptional Analysis of TH2 Primed Dendritic Cells and T cells

2021 ◽  
Author(s):  
◽  
Cynthia Morgan
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Cell Surface ◽  
Immune Responses ◽  
Rna Sequencing ◽  
Transcriptional Analysis ◽  
Th2 Cells ◽  
Nippostrongylus Brasiliensis ◽  
Sequencing Data ◽  
Th2 Response

<p><b>Allergy is a condition affecting between 10 and 30% of the world’s population, with incidence rising every year. It is primarily mediated by THelper (TH) 0 cells reacting to an ordinarily harmless environmental antigen to induce an adaptive TH2 response. TH0 cells are presented the antigen by dendritic cells (DC), the immune systems most proficient antigen presenting cell, which act as the bridge between the innate and adaptive immune system. Dendritic cells specific to this study termed Triple Negative (TN) and CD11b+ are able to prime T cells to become TH2 cells, but current research has been unable to fully determine the proteins that mediate this TH2 priming. TN and CD11b+ DC exhibit transcriptional and functional distinction within the TH2 response, but the individual functions they take on during TH2 responses have not fully been determined. Some evidence suggests that the cell surface protein OX40L and the secreted protein TSLP are capable of inducing TH2 priming, but this is not conserved across all TH2 models. In an effort to determine other specific proteins that induce TH2 priming, RNA-sequencing has been utilized on TN and CD11b+ dendritic cells in TH2 inducing conditions. This thesis aims to analyse RNA-sequencing data generated from purified TH2 antigen positive TN and CD11b+ dendritic cells that have taken up a TH2-inducing stimulus – fluorescently labelled (AF488) non-viable Nippostrongylus brasiliensis. Due to the majority of DC-TH0 interactions occurring at the cell surface interface, the bioinformatic analysis was focused on genes belonging to the surface and secreted compartments.</b></p> <p>Here I show that AF488-Nippostrongylus brasiliensis positive TN and CD11b+ DC are transcriptionally distinct from each other. Functional roles of differentially expressed genes (DEG) were also markedly distinct. Superfamily analysis revealed TN genes associated with signal transduction and proteases, whereas CD11b+ DEG were linked to cell adhesion and immune responses. This suggests that the different DC subsets have different roles in an immune response, and potentially different roles in the induction of TH2 immune responses. Network analysis of DEG from DC subsets and proteins expressed by TH0 and TH2 cell surfaces identified over 300 predicted interactions. Notably, 33 identified were known interactions – validating the bioinformatic methods used. Finally, I have been developing a method to assess novel interactions via flow cytometry methods that allows detection of binding and identification of the cell population that is bound. This has shown promise with the detection of generated proteins bound to TN and CD11b+ DC during TH2 stimulating conditions, paving the way for future novel interaction analyses.</p>

scholarly journals Concerted IL-25R and IL-4Rα signaling drive innate type 2 effector immunity for optimal helminth expulsion

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Katherine A Smith ◽  
Stephan Löser ◽  
Fumi Varyani ◽  
Yvonne Harcus ◽  
Henry J McSorley ◽  
...  
Keyword(s):  
Chronic Infection ◽  
Lymphoid Cells ◽  
Helminth Parasites ◽  
Wild Type ◽  
Heligmosomoides Polygyrus ◽  
Innate Effector ◽  
Interleukin 25 ◽  
Deficient Mice

Interleukin 25 (IL-25) is a major 'alarmin' cytokine, capable of initiating and amplifying the type immune response to helminth parasites. However, its role in the later effector phase of clearing chronic infection remains unclear. The helminth Heligmosomoides polygyrus establishes long-term infections in susceptible C57BL/6 mice, but is slowly expelled in BALB/c mice from day 14 onwards. We noted that IL-25R (Il17rb)-deficient BALB/c mice were unable to expel parasites despite type 2 immune activation comparable to the wild-type. We then established that in C57BL/6 mice, IL-25 adminstered late in infection (days 14–17) drove immunity. Moreover, when IL-25 and IL-4 were delivered to Rag1-deficient mice, the combination resulted in near complete expulsion of the parasite, even following administration of an anti-CD90 antibody to deplete innate lymphoid cells (ILCs). Hence, effective anti-helminth immunity during chronic infection requires an innate effector cell population that is synergistically activated by the combination of IL-4Rα and IL-25R signaling.

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