Hydronephrosis associated with antiurothelial and antinuclear autoantibodies in BALB/c-Fcgr2b
 −/−
 Pdcd1
 −/− mice

Okazaki, Taku; Otaka, Yumi; Wang, Jian; Hayashi, Hiroshi; Takai, Toshiyuki; Ravetch, Jeffrey V.; Honjo, Tasuku

doi:10.1084/jem.20051984

Cited by 48 publications

(49 citation statements)

References 28 publications

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“…In addition, programmed cell death 1 (PD-1) provides negative costimulation to lymphocytes. PD-1-deficient BALB/c mice spontaneously develop AIG (25,34), suggesting that PD-1-mediated signaling is critical for the negative regulation of AIG development. These regulatory mechanisms are primarily involved in suppressing the development of AIG, whereas although TSLP may be secondarily induced after triggering inflammation of AIG, induced TSLP did not regress the inflammation of AIG.…”

Section: Discussionmentioning

confidence: 99%

Increased Susceptibility to Autoimmune Gastritis in Thymic Stromal Lymphopoietin Receptor-Deficient Mice

Nishiura

Kido

Aoki

et al. 2012

The Journal of Immunology

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Thymic stromal lymphopoietin (TSLP), mainly produced by epithelial cells, activates a variety of cell types, including dendritic cells, mast cells, T cells, and B cells. It is involved in the pathogenesis of allergic inflammation in the lung, skin, and gastrointestinal tract. In addition, TSLP promotes Th2-type intestinal immunity against helminth infection and regulates Th1-type inflammation in a mouse model of colitis, suggesting that it plays crucial roles in intestinal immune homeostasis. Although autoimmune gastritis (AIG), mediated by inflammatory Th1 responses, develops in the gastric mucosa, it is not clear whether TSLP is involved in regulating these responses in AIG. The aim of this study was to examine the roles of TSLP in the development of AIG. Because BALB/c mice thymectomized 3 d after birth (NTx mice) develop AIG, we used this model to test the role of TSLP in the development of AIG. We found that in AIG-bearing mice, TSLP was expressed in the inflamed stomach and that the serum anti-parietal cell Ab levels in neonatal thymectomized TSLPR-deficient mice (NTx-TSLPR−/− mice) were significantly elevated over those in NTx-TSLPR+/+ mice. In addition, NTx-TSLPR−/− mice exhibited an earlier onset of AIG than that observed in NTx-TSLPR+/+ mice. The rapid development of AIG in NTx-TSLPR−/− mice resulted in more aggressive CD4+ T cell infiltration and more severe loss of parietal and chief cells in the progression phase of AIG, accompanied by enhanced production of IL-12/23p40 and IFN-γ. Taken together, these data suggested that TSLP negatively regulates the development of AIG.

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Section: Discussionmentioning

confidence: 99%

Increased Susceptibility to Autoimmune Gastritis in Thymic Stromal Lymphopoietin Receptor-Deficient Mice

Nishiura

Kido

Aoki

et al. 2012

The Journal of Immunology

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“…1,2 The critical role of PD-1 in the control of peripheral tolerance and lymphocyte activation is supported by the development of various autoimmune phenotypes in PD-1-deficient mice. [3][4][5][6][7][8] Co-inhibitory signals in lymphocytes are initiated by binding of PD-1 to its ligands PD-L1 (B7-H1) and PD-L2 (B7-DC). 9,10 Engagement of PD-1 results in the recruitment of the tyrosine phosphatase SHP-2, which dephosphorylates and inactivates proximal effector molecules such as Zap70 in T cells.…”

Section: Introductionmentioning

confidence: 99%

PD-1 expression on dendritic cells suppresses CD8⁺T cell function and antitumor immunity

et al. 2015

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Programmed death one (PD-1) is a well-established co-inhibitory regulator that suppresses proliferation and cytokine production of T cells. Despite remarkable progress in delineating the functional roles of PD-1 on T lymphocytes, little is known about the regulatory role of PD-1 expressed on myeloid cells such as dendritic cells (DCs). Here, we show that CD8C T cells can be more potently activated to secrete IL-2 and IFNg by PD-1-deficient DCs compared to wild-type DCs. Adoptive transfer of PD-1-deficient DCs demonstrated their superior capabilities in inducing antigen-specific CD8C T cell proliferation in vivo. In addition, we provide first evidence demonstrating the existence of peripheral blood DCs and CD11c

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“…It should be noted that no polyclonal activation of lymphocytes is observed in Pdcd1 Ϫ/Ϫ mice on either background, suggesting that PD-1 deficiency does not distort the general immune response. Taken together, Pdcd1 Ϫ/Ϫ mice may serve as a useful animal model to verify the effects of other genetic and environmental factors in the development of autoimmune diseases (17,18,21,22).…”

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confidence: 99%

PD-1 deficiency reveals various tissue-specific autoimmunity by H-2^band dose-dependent requirement of H-2^g7for diabetes in NOD mice

Yoshida¹,

Jiang²,

Honjo³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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Although many autoimmune diseases are associated with particular HLA/H-2 haplotypes, the mechanisms through which specific HLA/H-2 haplotypes afford autoimmune susceptibility remain enigmatic. Here, we analyzed the effects of the diabetes-associated (H-2 g7 ) and an antidiabetogenic (H-2 b ) H-2 haplotypes in NOD mice deficient for programmed cell death-1 (PD-1, Pdcd1), a unique model of type 1 diabetes that confers complete penetrance and rapid onset of the disease. NOD-H2 b/b Pdcd1 ؊/؊ mice were completely protected from diabetes, confirming that H-2 g7 is indispensable for diabetes even in the absence of PD-1. However, NOD-H2 b/b Pdcd1 ؊/؊ mice developed autoimmune inflammation in multiple tissues including peripheral nerves, stomachs, and exocrine tissues, demonstrating that autoreactive T cells are generated in the context of H-2 b . These autoreactive T cells damaged target tissues only in the absence of PD-1, confirming that PD-1 deficiency unravels the hidden autoimmune susceptibility of the strain by reducing the threshold of T cell activation. Transfer experiments revealed that CD4 T cells are the effector cells of neuritis, and nerve-infiltrating CD4 T cells are strongly deviated toward Th1. Interestingly, neuritogenic T cells were also generated in the context of H-2 g7 , in sharp contrast to the strict requirement of H-2 g7 for diabetes. In addition, 60% of the NOD-H2 b/g7 Pdcd1 ؊/؊ mice developed diabetes, suggesting that H-2 b does not dominantly suppress diabetes and that H-2 g7 induces diabetes in a dosedependent fashion.costimulation ͉ MHC ͉ PD-L1 ͉ polyneuropathy ͉ Th1/Th2

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Hydronephrosis associated with antiurothelial and antinuclear autoantibodies in BALB/c-Fcgr2b −/− Pdcd1 −/− mice

Cited by 48 publications

References 28 publications

Increased Susceptibility to Autoimmune Gastritis in Thymic Stromal Lymphopoietin Receptor-Deficient Mice

Increased Susceptibility to Autoimmune Gastritis in Thymic Stromal Lymphopoietin Receptor-Deficient Mice

PD-1 expression on dendritic cells suppresses CD8⁺T cell function and antitumor immunity

PD-1 deficiency reveals various tissue-specific autoimmunity by H-2^band dose-dependent requirement of H-2^g7for diabetes in NOD mice

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Hydronephrosis associated with antiurothelial and antinuclear autoantibodies in BALB/c-Fcgr2b −/− Pdcd1 −/− mice

Cited by 48 publications

References 28 publications

Increased Susceptibility to Autoimmune Gastritis in Thymic Stromal Lymphopoietin Receptor-Deficient Mice

Increased Susceptibility to Autoimmune Gastritis in Thymic Stromal Lymphopoietin Receptor-Deficient Mice

PD-1 expression on dendritic cells suppresses CD8+T cell function and antitumor immunity

PD-1 deficiency reveals various tissue-specific autoimmunity by H-2band dose-dependent requirement of H-2g7for diabetes in NOD mice

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PD-1 expression on dendritic cells suppresses CD8⁺T cell function and antitumor immunity

PD-1 deficiency reveals various tissue-specific autoimmunity by H-2^band dose-dependent requirement of H-2^g7for diabetes in NOD mice