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TL1A and allergic disease

Nidhi Malhotra, Juan Manuel Leyva-Castillo, Unmesh Jadhav, Olga Barreiro, Christy Kam, Nicholas K O'Neill, Francoise Meylan, Pierre Chambon, Ulrich H von Andrian, Richard M Siegel, Eddie C Wang, Ramesh Shivdasani, Raif S Geha
Atopic dermatitis is an allergic inflammatory skin disease characterized by the production of the type 2 cytokines in the skin by type 2 innate lymphoid cells (ILC2s) and T helper 2 (TH 2) cells, and tissue eosinophilia. Using two distinct mouse models of atopic dermatitis, we show that expression of retinoid-related orphan receptor α (RORα) in skin-resident T regulatory cells (Tregs ) is important for restraining allergic skin inflammation. In both models, targeted deletion of RORα in mouse Tregs led to exaggerated eosinophilia driven by interleukin-5 (IL-5) production by ILC2s and TH 2 cells...
March 2, 2018: Science Immunology
Ravinder Kaur Singh, William Victor Perks, Jason Peter Twohig, Emma J Kidd, Kenneth Broadley, Stuart N Farrow, Anwen Sian Williams, Philip Russel Taylor, Eddie Chung Yern Wang
The Death Receptor 3 (DR3)/Tumour Necrosis Factor-like cytokine 1A (TL1A) axis stimulates effector T cells and type 2 innate lymphocytes (ILC2) that trigger cytokine release and drive disease pathology in several inflammatory and autoimmune diseases, including murine models of acute allergic lung inflammation (ALI). The aim of this study was to elucidate the role of DR3 in chronic ALI compared to acute ALI, using mice genetically deficient in the DR3 gene (DR3ko ). Results showed DR3 expression in the lungs of wild-type mice was up-regulated following induction of acute ALI and this increased expression was maintained in chronic disease...
October 2017: Cellular Immunology
Françoise Meylan, Richard M Siegel
The tumor necrosis factor (TNF) receptors and their corresponding cytokine ligands have been implicated in many aspects of the biology of immune functions. TNF receptors have key roles during various stages of T cell homeostasis. Many of them can co-stimulate lymphocyte proliferation and cytokine production. Additionally, several TNF cytokines can regulate T cell differentiation, including promoting Th1, Th2, Th17, and more recently the newly described Th9 subset. Four TNF family cytokines have been identified as regulators for IL-9 production by T cells...
January 2017: Seminars in Immunopathology
Maya R Karta, David H Broide, Taylor A Doherty
Recent discoveries have led to the identification of a novel group of immune cells, the innate lymphoid cells (ILCs). The members of this group are divided into three subpopulations: ILC1s, ILC2s, and ILC3s. ILC2s produce Th2 cytokines, IL-4, IL-5, and IL-13, upon activation by epithelial cell-derived cytokines, lipid mediators (cysteinyl leukotrienes and prostaglandin D2), and TNF family member TL1A and promote structural and immune cell responses in the airways after antigen exposure. In addition, ILC2 function is also influenced by inducible T cell costimulator (ICOS)/ICOS-ligand (ICOS-L) interactions via direct contact between immune cells...
January 2016: Current Allergy and Asthma Reports
Arianne C Richard, John R Ferdinand, Françoise Meylan, Erika T Hayes, Odile Gabay, Richard M Siegel
Originally described in 2002 as a T cell-costimulatory cytokine, the tumor necrosis factor family member TNF-like factor 1A (TL1A), encoded by the TNFSF15 gene, has since been found to affect multiple cell lineages through its receptor, death receptor 3 (DR3, encoded by TNFRSF25) with distinct cell-type effects. Genetic deficiency or blockade of TL1A-DR3 has defined a number of disease states that depend on this cytokine-receptor pair, whereas excess TL1A leads to allergic gastrointestinal inflammation through stimulation of group 2 innate lymphoid cells...
September 2015: Journal of Leukocyte Biology
Arianne C Richard, Cuiyan Tan, Eric T Hawley, Julio Gomez-Rodriguez, Ritobrata Goswami, Xiang-Ping Yang, Anthony C Cruz, Pallavi Penumetcha, Erika T Hayes, Martin Pelletier, Odile Gabay, Matthew Walsh, John R Ferdinand, Andrea Keane-Myers, Yongwon Choi, John J O'Shea, Aymen Al-Shamkhani, Mark H Kaplan, Igal Gery, Richard M Siegel, Françoise Meylan
The TNF family cytokine TL1A (Tnfsf15) costimulates T cells and type 2 innate lymphocytes (ILC2) through its receptor DR3 (Tnfrsf25). DR3-deficient mice have reduced T cell accumulation at the site of inflammation and reduced ILC2-dependent immune responses in a number of models of autoimmune and allergic diseases. In allergic lung disease models, immunopathology and local Th2 and ILC2 accumulation is reduced in DR3-deficient mice despite normal systemic priming of Th2 responses and generation of T cells secreting IL-13 and IL-4, prompting the question of whether TL1A promotes the development of other T cell subsets that secrete cytokines to drive allergic disease...
April 15, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
F Meylan, E T Hawley, L Barron, J L Barlow, P Penumetcha, M Pelletier, G Sciumè, A C Richard, E T Hayes, J Gomez-Rodriguez, X Chen, W E Paul, T A Wynn, A N J McKenzie, R M Siegel
The tumor necrosis factor (TNF)-family cytokine TL1A (TNFSF15) costimulates T cells and promotes diverse T cell-dependent models of autoimmune disease through its receptor DR3. TL1A polymorphisms also confer susceptibility to inflammatory bowel disease. Here, we find that allergic pathology driven by constitutive TL1A expression depends on interleukin-13 (IL-13), but not on T, NKT, mast cells, or commensal intestinal flora. Group 2 innate lymphoid cells (ILC2) express surface DR3 and produce IL-13 and other type 2 cytokines in response to TL1A...
July 2014: Mucosal Immunology
Françoise Meylan, Arianne C Richard, Richard M Siegel
DR3 (TNFRSF25) is a member of the tumor necrosis factor receptor (TNFR) superfamily expressed primarily on lymphocytes and is a receptor for the TNF family cytokine TL1A (TNFSF15). DR3 costimulates T-cell activation, but it is unique among these receptors in that it signals through an intracytoplasmic death domain and the adapter protein TRADD (TNFR-associated death domain). TL1A costimulates T cells to produce a wide variety of cytokines and can promote expansion of activated and regulatory T cells in vivo...
November 2011: Immunological Reviews
Françoise Meylan, Todd S Davidson, Erin Kahle, Michelle Kinder, Krishika Acharya, Dragana Jankovic, Virgilio Bundoc, Marcus Hodges, Ethan M Shevach, Andrea Keane-Myers, Eddie C Y Wang, Richard M Siegel
DR3 (TRAMP, LARD, WSL-1, TNFRSF25) is a death-domain-containing tumor necrosis factor (TNF)-family receptor primarily expressed on T cells. TL1A, the TNF-family ligand for DR3, can costimulate T cells, but the physiological function of TL1A-DR3 interactions in immune responses is not known. Using DR3-deficient mice, we identified DR3 as the receptor responsible for TL1A-induced T cell costimulation and dendritic cells as the likely source for TL1A during T cell activation. Despite its role in costimulation, DR3 was not required for in vivo T cell priming, for polarization into T helper 1 (Th1), Th2, or Th17 effector cell subtypes, or for effective control of infection with Toxoplasma gondii...
July 18, 2008: Immunity
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