T helper (Th)1/Th2 balance determines the direction of some kinds of autoimmune diseases. The involvement of acini areas by CD4(+) helper T(Th) cell subset in submandibular and lacrimal glands are largely unknown in secondary Sjögren's syndrome (sSjS) with systemic lupus erythematosus (SLE). Submandibular and lacrimal glands were examined immunopathologically in lupus-prone female NZB × NZW(B/W)F(1) mice, model for human sSjS with SLE. Dacryoadenitis and sialoadenitis with renal failure developed with age. Infiltration of lymphoid cells (lymphocytes and plasma cells) expanded from the periductal areas in striated ducts to the acini, and the isolated foci in the acini were observed in those organs. The destruction of duct and acini epithelium, including the myoepithelium, was induced by interferon (IFN)-γ(+) and IgG2a(+) lymphoid cells, but not by interleukin(IL)-4(+), IL-5(+), IL-13(+), and IgG1(+) lymphoid cells. Compared with IL-5 and IL-13, high values of IFN-γ were produced systemically at various ages. Also local expression of IFN-γ mRNA was higher than that of IL-4 mRNA. The result suggests that the acini destruction in submandibular and lacrimal glands may be induced by systemic and local Th1 cell dominant reactions in lupus-prone B/WF(1) mice with sSjS.
"IFN-γ has been shown to be involved in goblet cell loss and epithelial apoptosis. It has been proposed as a biomarker for dry eye disease and SS, since elevated levels have been observed in protein and/or RNA in tears, saliva, conjunctiva, submandibular glands, blood,31,33–39 conjunctiva,39–42 saliva,43,44 lacrimal,4,45–50 submandibular glands,37,45,51–53 and blood.54,55 "
[Show abstract][Hide abstract] ABSTRACT: Dry eye from Sjögren's syndrome is a multifactorial disease that results in dysfunction of the lacrimal functional unit. Studies have shown changes in tear composition, including inflammatory cytokines, chemokines, and metalloproteinase. T-lymphocytes have been shown to increase in the conjunctiva and lacrimal glands in patient and animal models. This inflammation is in part responsible for the pathogenesis of the disease, which results in symptoms of eye irritation, ocular surface epithelial disease, and loss of corneal barrier function. There are a number of anti-inflammatory approaches for treating this disease. The current study reviews details of immune response and anti-inflammatory therapies used to control this disease.
[Show abstract][Hide abstract] ABSTRACT: Dry eye is an inflammatory disease that results from activation of innate inflammatory pathways in resident ocular surface cells, as well as cytokines produced by recruited T helper (Th) cells. Cytokines produced by the infiltrating Th cells alter the normal cytokine balance on the ocular surface and cause ocular surface epithelial pathology. Changes in levels of Th cytokines on the ocular surface have been measured in dry eye and the biological effects of these cytokines have been documented in experimental culture and mouse model systems. The Th2 cytokine IL-13 has a homeostatic role in promoting goblet cell differentiation. In contrast, The Th1 cytokine IFN-γ antagonizes IL-13 and promotes apoptosis and squamous metaplasia of the ocular surface epithelia. The Th17 cytokine, IL-17 promotes corneal epithelial barrier disruption. The ocular surface epithelium expresses receptors to all of these Th cytokines. Therapies that maintain normal IL-13 signaling, or suppress IFN- γ and IL-17 have potential for treating the ocular surface disease of dry eye.
Experimental Eye Research 09/2013; 117. DOI:10.1016/j.exer.2013.08.013 · 2.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Systemic lupus erythematosus (SLE) is a systemic multi-organ autoimmune disease with different immunological characteristics and clinical manifestations characterized by an autoantibody response to nuclear and cytoplasmic antigens; the etiology of this disease remains largely unknown. Most recent genome-wide association studies demonstrate that genetics significantly predispose to SLE onset, but the incomplete disease concordance rates between monozygotic twins indicates a role for other complementary factors in SLE pathogenesis. Recently, much evidence strongly supports other molecular mechanisms involved in the regulation of gene expression ultimately causing autoimmune disease, and several studies, both in clinical settings and experimental models, have demonstrated that epigenetic modifications may hold the key to a better understanding of SLE initiation and development. DNA methylation changes the structure of chromatin, being typically able to modulate the fine interactions between promoter-transcription factors and encoding genes within the transcription machinery. Alteration in DNA methylation has been confirmed as a major epigenetic mechanism that may potentially cause a breakdown of immune tolerance and perpetuation of SLE. Based on recent findings, DNA methylation treatments already being used in oncology may soon prove beneficial to patients with SLE. We herein discuss what we currently know, and what we expect in the future.
Maroof Hasan, Nicole Dobbs, Shaheen Khan, Michael A White, Edward K Wakeland, Quan-Zhen Li, Nan Yan
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