Modeling Sjögren's syndrome with Id3 conditional knockout mice

Guo, Zengli; Li, Hongmei; Han, Min; Xu, Tian; Wu, Xiaohui; Zhuang, Yuan

doi:10.1016/j.imlet.2010.09.009

Cited by 45 publications

(45 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous publications have confirmed that T cells play a critical role in disease initiation in Id3 −/− mice[7, 8], so we tested two key disease parameters in 12–24 week old Id3 −/− mice that lack αβ T cells, namely, lymphocytic infiltration and saliva production. Histological analysis of salivary gland tissues revealed that Id3 −/− mice lacking αβ T cells fail to develop the hallmark lymphocytic infiltration found in Id3 −/− mice (Figure 2A).…”

Section: Resultsmentioning

confidence: 99%

“…Altered glandular homeostasis has been reported in Id3 −/− mice prior to the presence of lymphocytic infiltration, suggesting that additional factors likely contribute to the early exocrinopathy observed in this SS mouse model[7]. T cells play an integral role in the initiation and progression of the pathogenesis observed in Id3 −/− mice, as shown through T cell transfer experiments and T cell specific deletion of Id3 −/− [7, 8]. It still remains unclear how T cells influence gland function prior to significant tissue infiltration.…”

Section: Introductionmentioning

confidence: 98%

See 1 more Smart Citation

Contribution of IL-13 to early exocrinopathy in Id3−/− mice

Mahlios

Zhuang

2011

Molecular Immunology

Self Cite

View full text Add to dashboard Cite

Id3−/− mice represent a model for T cell mediated primary Sjogren's syndrome (PSS). An intriguing feature of this disease model is the early appearance of impaired salivary function or exocrinopathy prior to lymphocytic infiltration of the salivary glands. This phenomenon prompted us to examine the role of cytokines produced by T cells in the systemic regulation of gland function. A comprehensive examination of serum cytokine profiles revealed elevated levels of IL-13 in Id3−/− mice. We found that the increase in serum IL-13 levels in Id3−/− mice was largely dependent on αβ T cells. Removal of αβ T cells in Id3−/− mice also eliminates disease symptoms, including lymphocytic infiltration in the gland tissues, and impaired saliva production. We further show that the number of mast cells in the salivary glands of Id3−/− mice is significantly increased, in a trend inversely related to the saliva production. This increase in the number of mast cells is also dependent on the presence of αβ T cells. Treatment of young Id3−/− mice with anti-IL-13 antibodies over a two-month period resulted in a reduction of both serum IL-13 levels and the number of mast cells in the salivary gland tissues, as well as correspondingly improved saliva production. These findings indicate a potentially important role for IL-13 in gland regulation and disease pathology.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Contribution of IL-13 to early exocrinopathy in Id3−/− mice

Mahlios

Zhuang

2011

Molecular Immunology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Csf1r MeriCreMer , Csf1r iCre , Rosa26 YFP-LSL , Cx 3 cr1 gfp/+ and Tnfrsf11a Cre mice (2, 5, 22, 35) and Id3 −/− ; Id1 fl/fl and Id3 f/f mice -kindly provided by R. Benezra (34, 36, 37)- were maintained under SPF conditions. Animal procedures were performed in adherence to our project licence issued by the United Kingdom Home Office under the Animals (Scientific Procedures) Act 1986 and by the Institutional Review Board (IACUC 15-04-006) from MSKCC.…”

Section: Methodsmentioning

confidence: 99%

Specification of tissue-resident macrophages during organogenesis

Mass

Ballesteros

Farlik

et al. 2016

Science

691

653

View full text Add to dashboard Cite

Resident macrophages support embryonic development and tissue homeostasis and repair. The mechanisms that control their differentiation remain unclear. We report here that Erythro-Myeloid Progenitors generate pre-macrophages (pMacs) that simultaneously colonize the whole embryo from embryonic day (E)9.5 in a chemokine-receptor dependent manner. The core macrophage program initiated in pMacs is rapidly diversified as expression of transcriptional regulators becomes tissue-specific in early macrophages. This process appears essential for macrophage specification and maintenance, as inactivation of Id3 impairs the development of liver macrophages and results in selective Kupffer cell deficiency in adults. We propose that macrophage differentiation is an integral part of organogenesis as colonization of organ anlagen by pMacs is followed by their specification into tissue macrophages, hereby generating the macrophage diversity observed in postnatal tissues.

show abstract

“…The ablation of T cells brought about by neonatal thymectomy in Id3 KO resulted in normal secretory function [122]. The T cell lineage-specific Id3 conditional knockout mouse (Id3 f/f ; LekCre) exhibited similar phenotypic features to the C57BL/6- Id3 −/− mouse model with the exception of anti-SSA/Ro and anti-SSB/La autoantibodies, suggesting that an acquired mutation in developing T cells may induce a SjS-like condition [123]. However, a clinical study reported that primary SjS patients, mainly Caucasians, showed normal Id3 gene expression in salivary glandular epithelial cells, labial salivary glands and peripheral T cells[124].…”

Section: Mouse Modelsmentioning

confidence: 99%

Mouse Models of Primary Sjogren’s Syndrome

Park¹,

Gauna²,

Cha

2015

CPD

View full text Add to dashboard Cite

Sjögren’s syndrome (SjS) is a chronic autoimmune disorder characterized by immune cell infiltration and progressive injury to the salivary and lacrimal glands. As a consequence, patients with SjS develop xerostomia (dry mouth) and keratoconjunctivitis sicca (dry eyes). SjS is the third most common rheumatic autoimmune disorder, affecting 4 million Americans with over 90% of patients being female. Current diagnostic criteria for SjS frequently utilize histological examinations of minor salivary glands for immune cell foci, serology for autoantibodies, and dry eye evaluation by corneal or conjunctival staining. SjS can be classified as primary or secondary SjS, depending on whether it occurs alone or in association with other systemic rheumatic conditions, respectively. Clinical manifestations typically become apparent when the disease is relatively advanced in SjS patients, which poses a challenge for early diagnosis and treatment of SjS. Therefore, SjS mouse models, because of their close resemblance to the human SjS, have been extremely valuable to identify early disease markers and to investigate underlying biological and immunological dysregulations. However, it is important to bear in mind that no single mouse model has duplicated all aspects of SjS pathogenesis and clinical features, mainly due to the multifactorial etiology of SjS that includes numerous susceptibility genes and environmental factors. As such, various mouse models have been developed in the field to try to recapitulate SjS. In this review, we focus on recent mouse models of primary SjS and describe them under three categories of spontaneous, genetically engineered, and experimentally induced development of SjS-like disease. In addition, we discuss future perspectives of SjS mouse models highlighting pros and cons of utilizing mouse models and demands for improved models.

show abstract

Modeling Sjögren's syndrome with Id3 conditional knockout mice

Cited by 45 publications

References 30 publications

Contribution of IL-13 to early exocrinopathy in Id3−/− mice

Contribution of IL-13 to early exocrinopathy in Id3−/− mice

Specification of tissue-resident macrophages during organogenesis

Mouse Models of Primary Sjogren’s Syndrome

Contact Info

Product

Resources

About