Autoimmunity against a Tissue Kallikrein in IQI/Jic Mice

Takada, Kouhei; Takiguchi, Mitsuyoshi; Konno, Akihiro; Inaba, Mutsumi

doi:10.1074/jbc.m410157200

Cited by 48 publications

(38 citation statements)

References 40 publications

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“…A minority of the genetically altered mice that develop a SLE-like disease also develop Sjögren's syndrome. Sjögren's syndrome is seen in NZW, (NZB ϫ NZW)F 1 , MRL/lpr, C3H/lpr, NFS/sld, aromatase-deficient mice and IQI/jic mice (81)(82)(83)(84)(85). All of these mice, like patients with Sjögren's disease, develop elevated serum IgM levels (81, 84 -86).…”

Section: Figurementioning

confidence: 99%

“…Furthermore, a minority of IL-14␣-transgenic mice develop Abs to Ro and La, autoantibodies that have been associated with the development of Sjögren's syndrome (88 -90). Murine models have suggested several other autoantigens may be important for the development Sjögren's syndrome (84,85,91). Which autoantigens are relevant to Sjögren's disease in IL-14␣-transgenic mice is an area of current investigation.…”

Section: Figurementioning

confidence: 99%

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Development of Autoimmunity in IL-14α-Transgenic Mice

Shen

Zhang

Wang

et al. 2006

The Journal of Immunology

110

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Multiple genetic loci contribute to the development of systemic lupus erythematosus (SLE). In murine models for SLE, various genes on chromosome four have been implicated. IL-14 is a cytokine originally identified as a B cell growth factor. The il14 gene is located on chromosome 4. IL-14α is a cytokine encoded by the plus strand of the IL-14 gene using exons 3–10. The expression of IL-14α is increased in (NZB × NZW)F1 mice. In this study, we produced IL-14α-transgenic mice to study the role of IL-14α in the development of autoimmunity. At age 3–9 mo, IL-14α-transgenic mice demonstrate increased numbers of B1 cells in the peritoneum, increased serum IgM, IgG, and IgG 2a and show enhanced responses to T-dependent and T-independent Ags compared with littermate controls. At age 9–17 mo, IL-14α-transgenic mice develop autoantibodies, sialadenitis, as in Sjögren’s syndrome, and immune complex-mediated nephritis, as in World Health Organization class II SLE nephritis. Between the ages 14–18 mo, 95% of IL-14α-transgenic mice developed CD5+ B cell lymphomas, consistent with the lymphomas seen in elderly patients with Sjögren’s syndrome and SLE. These data support a role for IL-14α in the development of both autoimmunity and lymphomagenesis. These studies may provide a genetic link between these often related disorders.

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Section: Figurementioning

confidence: 99%

Section: Figurementioning

confidence: 99%

Development of Autoimmunity in IL-14α-Transgenic Mice

Shen

Zhang

Wang

et al. 2006

The Journal of Immunology

110

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“…Type 3 muscarinic acetylcholine receptor was proposed based on the presence of autoreactive serum from dry eye patients (51), and excessive acetylcholine receptor stimulation was demonstrated to expose cryptic type 3 muscarinic acetylcholine receptor epitopes to be sampled by APCs (52). Putative autoantigens were also identified from the kallikrein family, namely Klk13 and Klk1b22 (53,54). Nonetheless, identifying the specific initiating autoantigen is fundamentally difficult and still remains elusive among the vast spectrum of organ-specific autoimmune diseases.…”

Section: Cd11bmentioning

confidence: 99%

Ocular Surface APCs Are Necessary for Autoreactive T Cell-Mediated Experimental Autoimmune Lacrimal Keratoconjunctivitis

Schaumburg

Siemasko

Paiva

et al. 2011

The Journal of Immunology

134

126

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As specialized sentinels between the innate and adaptive immune response, APCs are essential for activation of Ag-specific lymphocytes, pathogen clearance, and generation of immunological memory. The process is tightly regulated; however, excessive or atypical stimuli may ignite activation of APCs in a way that allows self-Ag presentation to autoreactive T cells in the context of the necessary costimulatory signals, ultimately resulting in autoimmunity. Studies in both animal models and patients suggest that dry eye is a chronic CD4+ T cell-mediated ocular surface autoimmune-based inflammatory disease. Using a desiccating stress-induced mouse model of dry eye, we establish the fundamental role of APCs for both the generation and maintenance of ocular-specific autoreactive CD4+ T cells. Subconjunctival administration of liposome-encapsulated clodronate efficiently diminished resident ocular surface APCs, inhibited the generation of autoreactive CD4+ T cells, and blocked their ability to cause disease. APC-dependent CD4+ T cell activation required intact draining cervical lymph nodes, as cervical lymphadenectomy also inhibited CD4+ T cell-mediated dry eye disease. In addition, local depletion of peripheral conjunctival APCs blocked the ability of dry eye-specific CD4+ T cells to accumulate within the ocular surface tissues, suggesting that fully primed and targeted dry eye-specific CD4+ T cells require secondary activation by resident ocular surface APCs for maintenance and effector function. These data demonstrate that APCs are necessary for the initiation and development of experimental dry eye and support the standing hypothesis that dry eye is a self-Ag–driven autoimmune disease.

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“…Total RNAs were prepared, reverse-transcribed into cDNAs as described previously [18], and amplified by polymerase chain reaction (PCR) for claudins 1-4, 8, 10, 11, and 16, occludin, ZO-1, and glyceraldehyde 3-phosphate dehydrogenase. The amplified cDNA fragments were confirmed by sequencing on a CEQ8800 DNA analysis system (Beckman Coulter, Fullerton, CA, U.S.A.).…”

Section: Antibodiesmentioning

confidence: 99%

Developmental Changes in the Expression of Tight Junction Protein Claudins in Murine Metanephroi and Embryonic Kidneys

Ohta

Adachi

Inaba

2006

The Journal of Veterinary Medical Science

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ABSTRACT. Claudins are the major constituents of tight junction (TJ) strands and participate in the cell-cell adhesion and permeability barrier in epithelial cell layers. To investigate the suitability of metanephroi for analysis of the function of the TJ protein claudins in renal tubular formation, mouse metanephroi from embryos at day 12 of gestation were cultured and expression of claudins was compared with that in embryonic kidneys. During in vitro culture for 8 days, the metanephroi showed expression patterns very similar to those observed in embryonic kidneys in reverse transcription-polymerase chain reaction for the claudins examined, including claudins 1-4, 8, 10, 11, and 16, and the TJ proteins occludin and ZO-1. Immunofluorescence microscopy for claudins 1-4, 8, 10, and 16 showed localization of these claudins at the TJ with occludin and ZO-1 in some restricted tubular segments. These findings indicate that the metanephroi show developmental changes in the expression of the TJ protein claudins, representing those in embryonic kidneys, and thus suggest that the mouse metanephros is suitable to examine the functions of specific claudins in the kidney. KEY WORDS: claudin, metanephroi, mouse, renal tubule, tight junction.The tight junction (TJ) is located at the apicalmost region of the lateral membrane of the epithelial cell, and plays a critical role in sealing the intercellular space in epithelial cellular sheets. The TJ behaves as the primary barrier to the diffusion of solutes and water through the paracellular pathway and maintains cell polarity as a boundary between the apical and basolateral plasma membrane domains [6,16,19,20]. In freeze-fracture replicas of epithelial cells, TJs appear as a continuous anastomosing network of intramembranous particle strands, i.e., TJ strands. The major components of TJ strands are the integral membrane proteins occludin and claudins, and some cytoplasmic scaffolding proteins such as ZO-1 which anchor occludin and claudins to actin filaments [20]. The claudins are a family of more than 20 homologous subtypes which share the same membrane topology and have various tissue-specific and segment-specific distribution patterns [19,20]. Heterogenous claudins form individual TJ strands as heteropolymers to adhere to each other at the cell-cell interface [4] to generate consequential variations in the tightness of individual TJ strands [19].Pathological phenotypes of humans and animals with mutations in genes of specific claudins, including claudins 11 [5], 14 [2,22], and 16 [7,11,17], demonstrate the importance of these TJ proteins in the formation and maintenance of epithelial architecture. However, the precise mechanisms for degeneration of cells and tissues in these diseases remain unknown. CLDN16 gene mutations cause familial hypomagnesemia with hypercalciuria and nephrocalcinosis in the human [17] and renal tubular dysplasia with interstitial nephritis in cattle [7,11] . This putative function of claudin-16 appears to be indispensable and not compensated for by the ...

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Autoimmunity against a Tissue Kallikrein in IQI/Jic Mice

Cited by 48 publications

References 40 publications

Development of Autoimmunity in IL-14α-Transgenic Mice

Development of Autoimmunity in IL-14α-Transgenic Mice

Ocular Surface APCs Are Necessary for Autoreactive T Cell-Mediated Experimental Autoimmune Lacrimal Keratoconjunctivitis

Developmental Changes in the Expression of Tight Junction Protein Claudins in Murine Metanephroi and Embryonic Kidneys

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