title: Aberrant production of IL-13 by T cells promotes exocrinopathy in Id3 knockout mice.
abstract: Elevated levels of the cytokine IL-13 has been found to be associated with autoimmune diseases, including Sjögren's Syndrome. However, whether IL-13 plays a causative role in disease development is not known and cannot be easily studied in humans. Our previous work has shown that levels of IL-13 are elevated in Id3 knockout mice, which has been established as a model for primary Sjögren's Syndrome. Here, we utilized an IL-13 reporter to determine the source of the elevated IL-13 levels observed in Id3 knockout mice and assess its contribution to SS pathology. Our results indicate that T cells, notably CD4 and γδ T cells, in Id3 knockout mice acquire IL-13 competency at an elevated rate well before disease symptoms become apparent. We also show that T cells developing early in life are more predisposed to produce IL-13. Finally, analysis of Id3 and IL-13 double deficient mice demonstrated that IL-13 plays an essential role in the deterioration of gland function. Our study provides crucial genetic evidence that enhanced IL-13 production by T cells can play a causative role in the exocrinopathy observed in Id3 knockout mice.
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Ian
authors.initials: I
authors.lastname: Belle
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Josh
authors.initials: J
authors.lastname: Mahlios
authors.affiliation: MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: McKenzie
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA. Electronic address: yzhuang@duke.edu.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhuang
mesh_terms: D000375:Aging / Q000276:immunology; D000818:Animals; D000831:Animals, Newborn; D005088:Exocrine Glands / Q000378:metabolism / Q000473:pathology*; D051796:Inhibitor of Differentiation Proteins / Q000172:deficiency* / Q000378:metabolism; D018793:Interleukin-13 / Q000096:biosynthesis*; D018345:Mice, Knockout; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D012469:Salivary Glands / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000378:metabolism*; D060168:Thymocytes / Q000378:metabolism
chemical_list: D051796:Inhibitor of Differentiation Proteins; D018793:Interleukin-13; D016692:Receptors, Antigen, T-Cell, gamma-delta; C067679:Idb3 protein, mouse
keywords: CD4 T cells; IL-13; Id3; Sjögren’s Syndrome; γδ T cells