Aberrant MHC class II expression in mouse joints leads to arthritis with extraarticular manifestations similar to rheumatoid arthritis

Kanazawa, Susumu; Ota, Satoshi; Sekine, Chiyoko; Tada, Toyohiro; Otsuka, Takanobu; Okamoto, Takashi; Sønderstrup, Grete; Peterlin, B. Matija

doi:10.1073/pnas.0606450103

Cited by 33 publications

(57 citation statements)

References 40 publications

(41 reference statements)

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“…Our findings are in contrast to two other models of autoimmune arthritis that reported an association with autoimmune arthritis-related inflammation and fibrotic lung disease (34,40,41). These models promoted autoimmune arthritis via different mechanisms, one through altering T-cell signaling with a mutation in zeta chain-associated protein kinase 70 (ZAP-70) (SKG mice), and the other via aberrant MHC Class II expression.…”

contrasting

confidence: 54%

Autoreactive T and B Cells Induce the Development of Bronchus-Associated Lymphoid Tissue in the Lung

Shilling¹,

Williams²,

Perera³

et al. 2013

Am J Respir Cell Mol Biol

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Rheumatoid arthritis-related interstitial lung disease (RA-ILD) is associated with significant morbidity and mortality. Studies in humans have found that the incidence of bronchus-associated lymphoid tissue (BALT) correlates with the severity of lung injury. However, the mechanisms underlying the development of BALT during systemic autoimmunity remain unknown. We have determined whether systemic autoimmunity in a murine model of autoimmune arthritis can promote the development of BALT by generating a novel murine model derived from K/BxN mice. Transgenic mice with the KRN T-cell receptor specific for the autoantigen, glucose-6-phosphate isomerase (GPI), were crossed with GPI-specific immunoglobulin heavy and light chain knock-in mice, producing mice with a majority of T and B cells specific for the same autoantigen. We found that 67% of these mice demonstrated lymphocytic infiltration in the lungs, localized to either the perivascular or peribronchial regions. Fifty percent of the mice with lymphocytic infiltration manifested lymphoid-like lesions resembling BALT, with distinct T and B cell follicles. The lungs from mice with lymphoid infiltrates had increased numbers of cytokine-producing T cells, including IL-17A1 T cells and increased major histocompatibility complex Class II expression on B cells. Interestingly, challenge with bleomycin failed to elicit a significant fibrotic response, compared with wild-type control mice. Our data suggest that systemic autoreactivity promotes ectopic lymphoid tissue development in the lung through the cooperation of autoreactive T and B cells. However, these BALT-like lesions may not be sufficient to promote fibrotic lung disease at steady state or after inflammatory challenge.

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contrasting

confidence: 54%

Autoreactive T and B Cells Induce the Development of Bronchus-Associated Lymphoid Tissue in the Lung

Shilling¹,

Williams²,

Perera³

et al. 2013

Am J Respir Cell Mol Biol

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“…27,28) For human low attenuation area was determined as lower Ϫ900 HU. 9,18) However, studies reveal lowest value is Ϫ800 HU and never reached Ϫ950 HU in murine emphysematous lung. 29,30) In addition, mean density of murine normal lung is around Ϫ500 to Ϫ600 HU by ours and Plathow et al 20) and around Ϫ400 HU, 20,29,30) which is quite different from that of human (Ϫ700 HU).…”

Section: Discussionmentioning

confidence: 99%

“…9) Anesthesia using ketamine and xylazine induces weak and reduced respiration. The calibration of the CT is conducted using the standard phantom followed by manufacture's instruction.…”

Section: Methodsmentioning

confidence: 99%

“…8) High respiration rates of mice cause difficulty for high quality of images of the lung. Although invasive methods using tracheostomy enable high quality images, 9,10) we employed free-breathing method to take the images serially in a deeply-anesthetized condition, in which respiration rates were reduced. The purpose of present study is to clarify whether the kinetics of a murine elastase-induced emphysema model can be assessed using CT and to compare the results with morphological analysis.…”

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confidence: 99%

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Sequential and Quantitative Analysis of a Murine Model of Elastase-Induced Emphysema

Kawakami

Matsuo

Yoshiura

et al. 2008

Biological & Pharmaceutical Bulletin

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Chronic obstructive pulmonary disease (COPD) is one of the serious causative diseases in death of aging people.1) Emphysema, one of COPD, is characterized as destruction of airway wall and small airway inflammation.1) An imbalance between elastinolytic proteases and their natural inhibitors is thought to play a role in the pathogenesis of emphysema. One animal model of emphysema is made by administrating of elastase into the lungs.2-4) Cigarette smoke-induced emphysema is another common model of emphysema. A study of elastase-deficient mice has revealed that elastase is also critical in smoke-induced emphysema.5) As several months are required to establish cigarette smoke-induced emphysema, the elastase-induced model is more convenient for assessing drug effects.To quantitatively assess the murine model of emphysema, historical assessment using mean linear intercept (Lm) has been used. 6) Because the elastase-induced destruction of airway wall is not homogenous, random several views are taken to estimate the destruction.The non-homogenous region of the disease is also applicable for human. In human, noninvasive computed tomography (CT) is commonly used for diagnosis and disease staging by assessing areas of low attenuation.1,7) The primary benefits of CT monitoring are the ability to assess the lungs in their entirety and the ability to follow the same mice over time.Micro-computed tomography has been developed, resulting in low-noise CT images in a small animal. CT images are used to follow-up tumor growth in the lung.8) High respiration rates of mice cause difficulty for high quality of images of the lung. Although invasive methods using tracheostomy enable high quality images, 9,10) we employed free-breathing method to take the images serially in a deeply-anesthetized condition, in which respiration rates were reduced. The purpose of present study is to clarify whether the kinetics of a murine elastase-induced emphysema model can be assessed using CT and to compare the results with morphological analysis. MATERIALS AND METHODSAdministration of Elastase C57BL/6N mice were obtained from Charles River Japan (Kanagawa, Japan) and bred in the animal facilities of Musashino University School of Medicine under specific pathogen-free (SPF) conditions. Care and use of animals followed the guidelines of the "Principles of Laboratory Animal Care" formulated by the National Society for Medical Research.Four cycles of sequential CT analysis were performed using 26 mice, six of which were also under histological examination at the end points. For histological analysis only, 12 mice were used for each time points, and in 8 different time points were examined. Another six mice were employed under CT and histological analysis once at the same day.Mice were anesthetized with ether or intraperitoneal injection of ketamine (90 mg/kg) and xylazine (1 mg/kg) and given intranasal administration of 0.3 or 1.2 units of porcine pancreatic elastase (Sigma-Aldrich, St. Louis, MO, U.S.A.) in 30 ml saline solution. Control mice were intra...

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“…[1][2][3] Once immune recognition has begun, the aberrant expression of MHC class II on nonprofessional Ag-presenting cells can facilitate disease progression and yield a more severe disease. 39,40 Aberrant expression of MHC class II molecules has been revealed in response to IFN-␥, IL-4, and IL-10. 18,41 In the present study using normal B6 mice, a relatively modest but functionally significant increase in type IV CIITA, and MHC class II expression in the salivary and lacrimal gland epithelial cells at 3 weeks after ovariectomy was detected, and thereafter declined with age, indicating that the steroid-related hormonal compensation occurred in vivo.…”

Section: Discussionmentioning

confidence: 99%

Role of Plasmacytoid Dendritic Cells for Aberrant Class II Expression in Exocrine Glands from Estrogen-Deficient Mice of Healthy Background

Arakaki

Nagaoka

Ishimaru

et al. 2009

The American Journal of Pathology

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Although it has been well documented that aberrant major histocompatibility complex class II molecules may contribute to the development of autoimmune disorders, the precise mechanisms responsible for their tissue-specific expression remain unknown. Here we show that estrogen deficiency induces aberrant class II major histocompatibility complex expression in exocrine glands via interactions between epithelial cells and plasmacytoid dendritic cells. Relatively modest but functionally significant expression levels of major histocompatibility complex class II and class II transactivator molecules were observed in the exocrine glands of ovariectomized (Ovx) C57BL/6 (B6) mice, but were not seen in the exocrine glands of control B6 mice. We observed that the salivary dendritic cells adjacent to the apoptotic epithelial cells positive for terminal deoxynucleotidyl transferasemediated dUTP nick-end labeling, were activated in Ovx mice, but were not activated in control mice. We obtained evidence that the salivary gland cells express both interferon regulatory factor-1 and class II transactivator type IV molecules in Ovx mice. Major histocompatibility complex (MHC) class II molecules are crucial for restricting immune reactivity to self versus foreign antigens during thymic education, and their expression level is essential for determining T cell activation in the periphery.1-3 MHC class II molecules are basically expressed on antigen (Ag)-presenting cells of the hematopoietic lineage, but can be induced by unknown stimuli on many other cell types (such as endothelial cells, hepatocytes, pancreatic ␤-cells, thyrocytes, and salivary gland cells) in association with autoimmunity.4 -10 MHC class II proteins play a central role in the control of normal immune homeostasis, while aberrant expression of MHC class II is frequently associated with abnormalities in immune responses.11-13 MHC class II expression is regulated by multiple cytokines, including interferon (IFN)-␥, which can enhance the immune response by upregulating MHC class II expression in immune cells, in addition to inducing Ag-presentation capacity.14,15 It is well known that the induction of MHC class II gene transcription by IFN-␥ is mediated by the MHC class II transactivator (CIITA), and depends on the presence of two transcription factors; signal transducer and activator of transcription 1 and interferon regulatory factor (IRF-1). 16 CIITA is a true co-activator because it does not bind directly to DNA but mediates its function on the class II MHC promoter through interaction with other proteins. 17,18 It is considered a master regulator because it is necessary and sufficient for the expression of all of the genes in the MHC class II pathway. Although recent studies have begun to reveal that epigenetic mechanisms have a key role in activating CIITA expression in normal cells, 19 the factors regulating this promoter have yet to be investigated.

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Aberrant MHC class II expression in mouse joints leads to arthritis with extraarticular manifestations similar to rheumatoid arthritis

Cited by 33 publications

References 40 publications

Autoreactive T and B Cells Induce the Development of Bronchus-Associated Lymphoid Tissue in the Lung

Autoreactive T and B Cells Induce the Development of Bronchus-Associated Lymphoid Tissue in the Lung

Sequential and Quantitative Analysis of a Murine Model of Elastase-Induced Emphysema

Role of Plasmacytoid Dendritic Cells for Aberrant Class II Expression in Exocrine Glands from Estrogen-Deficient Mice of Healthy Background

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