title: Enteric nematodes and the path to up-regulation of type 2 cytokines IL-4 and IL-13.
abstract: Protective immunity against enteric parasitic nematodes is dependent on IL-4, IL-13 activation of their exclusive transcription factor STAT6. The precise pathways by which enteric parasitic nematodes are recognized by the host is unclear, but elimination of this important interaction in developed nations is thought to contribute to the dysregulated immune responses that are a characteristic of autoimmune diseases. Nematode-derived products are involved in evading host defenses to promote their life cycle leading to modulation of host immune responses. Host protective immunity has adapted to enteric parasitic nematode infection by elaboration of mucins, increasing intraluminal fluid to control access to the surface epithelium, increasing cell turnover to maintain an effective barrier to their invasion, initiating immune responses through activation of resident immune cells, and recruitment of additional immune cells to release immune mediators that help orchestrate these responses. Both the immune and functional outcomes depend largely on IL-4/IL-13 signaling through STAT6, with a dominant role for IL-13 working through the type 2 IL-4 receptor (IL-4R). The recent observation that enteric nematode infection prevents the onset of a number of experimental models of IBD, diabetes, and several extraintestinal autoimmune diseases including multiple sclerosis has generated considerable interest in the identification of worm/egg products involved in the generation and maintenance of Th2 cytokines that may mediate the beneficial effects of nematode infection in autoimmune and inflammatory pathologies.
authors.affiliation: Dept. of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD 21201, United States; Dept. of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, United States. Electronic address: tdonohue@som.umaryland.edu.
authors.forename: Terez
authors.initials: T
authors.lastname: Shea-Donohue
authors.affiliation: Dept. of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD 21201, United States.
authors.forename: Rex
authors.initials: R
authors.lastname: Sun
authors.affiliation: Dept. of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, United States.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Bohl
authors.affiliation: Dept. of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, United States.
authors.forename: Leon P
authors.initials: LP
authors.lastname: McLean
authors.affiliation: Dept. of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD 21201, United States; Dept. of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, United States.
authors.forename: Aiping
authors.initials: A
authors.lastname: Zhao
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology; D003921:Diabetes Mellitus, Experimental; D019281:Dimerization; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006801:Humans; D007107:Immune System; D015212:Inflammatory Bowel Diseases / Q000276:immunology; D018793:Interleukin-13 / Q000276:immunology*; D015847:Interleukin-4 / Q000276:immunology*; D007413:Intestinal Mucosa / Q000276:immunology / Q000469:parasitology*; D051379:Mice; D009103:Multiple Sclerosis / Q000276:immunology; D009348:Nematoda; D009349:Nematode Infections / Q000276:immunology / Q000469:parasitology*; D019948:Receptors, Interleukin-4 / Q000378:metabolism; D050800:STAT6 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic; D015854:Up-Regulation
chemical_list: D018793:Interleukin-13; D019948:Receptors, Interleukin-4; D050800:STAT6 Transcription Factor; D015847:Interleukin-4
keywords: Enteric nematodes; IL-13; IL-4; STAT6 genes; Worm-derived products