scholarly journals Trefoil factor 2 rapidly induces interleukin 33 to promote type 2 immunity during allergic asthma and hookworm infection

2012 ◽  
Vol 209 (3) ◽  
pp. 607-622 ◽  
Author(s):  
Marsha Wills-Karp ◽  
Reena Rani ◽  
Krista Dienger ◽  
Ian Lewkowich ◽  
James G. Fox ◽  
...  
Keyword(s):  
Messenger Rna ◽  
Molecular Mechanisms ◽  
Nippostrongylus Brasiliensis ◽  
Trefoil Factor ◽  
Interleukin 33 ◽  
Parasitic Helminths ◽  
Type 2 Immunity ◽  
Th2 Responses ◽  
Trefoil Factor 2

The molecular mechanisms that drive mucosal T helper type 2 (TH2) responses against parasitic helminths and allergens remain unclear. In this study, we demonstrate in mice that TFF2 (trefoil factor 2), an epithelial cell–derived repair molecule, is needed for the control of lung injury caused by the hookworm parasite Nippostrongylus brasiliensis and for type 2 immunity after infection. TFF2 is also necessary for the rapid production of IL-33, a TH2-promoting cytokine, by lung epithelia, alveolar macrophages, and inflammatory dendritic cells in infected mice. TFF2 also increases the severity of allergic lung disease caused by house dust mite antigens or IL-13. Moreover, TFF2 messenger RNA expression is significantly increased in nasal mucosal brushings during asthma exacerbations in children. These experiments extend the biological functions of TFF2 from tissue repair to the initiation and maintenance of mucosal TH2 responses.

scholarly journals Trefoil Factor 2 Promotes Type 2 Immunity and Lung Repair through Intrinsic Roles in Hematopoietic and Nonhematopoietic Cells

2018 ◽  
Vol 188 (5) ◽  
pp. 1161-1170 ◽  
Author(s):  
Li-Yin Hung ◽  
Taylor K. Oniskey ◽  
Debasish Sen ◽  
Matthew F. Krummel ◽  
Andrew E. Vaughan ◽  
...  
Keyword(s):  
Trefoil Factor ◽  
Lung Repair ◽  
Type 2 Immunity ◽  
Intrinsic Roles ◽  
Trefoil Factor 2

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 Schistosome-derived omega-1 drives Th2 polarization by suppressing protein synthesis following internalization by the mannose receptor

2012 ◽  
Vol 209 (10) ◽  
pp. 1753-1767 ◽  
Author(s):  
Bart Everts ◽  
Leonie Hussaarts ◽  
Nicole N. Driessen ◽  
Moniek H.J. Meevissen ◽  
Gabriele Schramm ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Protein Synthesis ◽  
Messenger Rna ◽  
Molecular Mechanisms ◽  
Mannose Receptor ◽  
Site Directed Mutagenesis ◽  
Directed Mutagenesis ◽  
Th2 Polarization ◽  
Th2 Responses ◽  
Egg Antigen

Omega-1, a glycosylated T2 ribonuclease (RNase) secreted by Schistosoma mansoni eggs and abundantly present in soluble egg antigen, has recently been shown to condition dendritic cells (DCs) to prime Th2 responses. However, the molecular mechanisms underlying this effect remain unknown. We show in this study by site-directed mutagenesis of omega-1 that both the glycosylation and the RNase activity are essential to condition DCs for Th2 polarization. Mechanistically, we demonstrate that omega-1 is bound and internalized via its glycans by the mannose receptor (MR) and subsequently impairs protein synthesis by degrading both ribosomal and messenger RNA. These experiments reveal an unrecognized pathway involving MR and interference with protein synthesis that conditions DCs for Th2 priming.

scholarly journals Acetylcholine production by group 2 innate lymphoid cells promotes mucosal immunity to helminths

2021 ◽  
Vol 6 (57) ◽  
pp. eabd0359
Author(s):  
Luke B. Roberts ◽  
Corinna Schnoeller ◽  
Rita Berkachy ◽  
Matthew Darby ◽  
Jamie Pillaye ◽  
...  
Keyword(s):  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Mucosal Barrier ◽  
Nippostrongylus Brasiliensis ◽  
Interleukin 33 ◽  
Group 2 ◽  
Maximal Induction

Innate lymphoid cells (ILCs) are critical mediators of immunological and physiological responses at mucosal barrier sites. Whereas neurotransmitters can stimulate ILCs, the synthesis of small-molecule neurotransmitters by these cells has only recently been appreciated. Group 2 ILCs (ILC2s) are shown here to synthesize and release acetylcholine (ACh) during parasitic nematode infection. The cholinergic phenotype of pulmonary ILC2s was associated with their activation state, could be induced by in vivo exposure to extracts of Alternaria alternata or the alarmin cytokines interleukin-33 (IL-33) and IL-25, and was augmented by IL-2 in vitro. Genetic disruption of ACh synthesis by murine ILC2s resulted in increased parasite burdens, lower numbers of ILC2s, and reduced lung and gut barrier responses to Nippostrongylus brasiliensis infection. These data demonstrate a functional role for ILC2-derived ACh in the expansion of ILC2s for maximal induction of type 2 immunity.

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