scholarly journals CD22 × Siglec-G Double-Deficient Mice Have Massively Increased B1 Cell Numbers and Develop Systemic Autoimmunity

2010 ◽  
Vol 184 (7) ◽  
pp. 3618-3627 ◽  
Author(s):  
Julia Jellusova ◽  
Ute Wellmann ◽  
Kerstin Amann ◽  
Thomas H. Winkler ◽  
Lars Nitschke
Keyword(s):  
Cell Numbers ◽  
Systemic Autoimmunity ◽  
Deficient Mice

scholarly journals Development of self-reactive germinal center B cells and plasma cells in autoimmune FcγRIIB-deficient mice

2010 ◽  
Vol 207 (12) ◽  
pp. 2767-2778 ◽  
Author(s):  
Thomas Tiller ◽  
Juliane Kofer ◽  
Cornelia Kreschel ◽  
Christian E. Busse ◽  
Stefan Riebel ◽  
...  
Keyword(s):  
B Cells ◽  
Germinal Center ◽  
Plasma Cells ◽  
Cell Compartment ◽  
Fc Gamma Receptor ◽  
Gamma Receptor ◽  
Systemic Autoimmunity ◽  
Bone Marrow Plasma ◽  
Ig G ◽  
Deficient Mice

Abnormalities in expression levels of the IgG inhibitory Fc gamma receptor IIB (FcγRIIB) are associated with the development of immunoglobulin (Ig) G serum autoantibodies and systemic autoimmunity in mice and humans. We used Ig gene cloning from single isolated B cells to examine the checkpoints that regulate development of autoreactive germinal center (GC) B cells and plasma cells in FcγRIIB-deficient mice. We found that loss of FcγRIIB was associated with an increase in poly- and autoreactive IgG+ GC B cells, including hallmark anti-nuclear antibody–expressing cells that possess characteristic Ig gene features and cells producing kidney-reactive autoantibodies. In the absence of FcγRIIB, autoreactive B cells actively participated in GC reactions and somatic mutations contributed to the generation of highly autoreactive IgG antibodies. In contrast, the frequency of autoreactive IgG+ B cells was much lower in spleen and bone marrow plasma cells, suggesting the existence of an FcγRIIB-independent checkpoint for autoreactivity between the GC and the plasma cell compartment.

scholarly journals Surfactant metabolic consequences of overexpression of GM-CSF in the epithelium of GM-CSF-deficient mice

1997 ◽  
Vol 273 (4) ◽  
pp. L709-L714 ◽  
Author(s):  
Machiko Ikegami ◽  
Alan H. Jobe ◽  
Jacquelyn A. Huffman Reed ◽  
Jeffrey A. Whitsett
Keyword(s):  
Lung Tissue ◽  
Surfactant Protein ◽  
Type Ii ◽  
Cell Numbers ◽  
Gm Csf ◽  
Type Ii Cell ◽  
Macrophage Colony ◽  
Respiratory Epithelial ◽  
Deficient Mice ◽  
Surfactant Metabolism

Granulocyte macrophage colony-stimulating factor (GM-CSF) is a regulator of surfactant metabolism because GM-CSF-deficient mice have abnormally slow clearance and catabolism of saturated phosphatidylcholine (Sat PC) and surfactant protein (SP)-A in airspaces and lung tissue. Overexpression of GM-CSF only in respiratory epithelial cells of mice deficient in GM-CSF using the SP-C promotor (GM−/−,SP-C-GM+/+) resulted in increased type II cell numbers and normalization of alveolar Sat PC pool sizes. Metabolic measurements demonstrated that incorporation of radiolabeled choline and palmitate was increased more than twofold, but the amount of radiolabeled Sat PC that accumulated in airspaces relative to the amount incorporated was decreased by 50% relative to normal GM+/+ mice. The clearance of dipalmitoylphosphatidylcholine and SP-B from the airspaces was more rapid for GM−/−,SP-C-GM+/+ mice than for GM+/+ mice. Loss of Sat PC and SP-B from the lungs (alveolar plus lung tissue) was similar in the two strains of mice. The normal surfactant pools in the GM−/−,SP-C-GM+/+ mice were achieved by the net effects of increases in type II cell numbers, increased incorporation, decreased accumulation, and increased reuptake rates for surfactant components, demonstrating the multiple effects of GM-CSF on surfactant metabolism.

scholarly journals CD137-Deficient Mice Have Reduced NK/NKT Cell Numbers and Function, Are Resistant to Lipopolysaccharide-Induced Shock Syndromes, and Have Lower IL-4 Responses

2004 ◽  
Vol 173 (6) ◽  
pp. 4218-4229 ◽  
Author(s):  
Dass S. Vinay ◽  
Beom K. Choi ◽  
Jun S. Bae ◽  
Won Y. Kim ◽  
Bryan M. Gebhardt ◽  
...  
Keyword(s):  
Nkt Cell ◽  
Cell Numbers ◽  
And Function ◽  
Deficient Mice

Tetraspanin CD53 modulates lymphocyte trafficking but not systemic autoimmunity in Lyn‐deficient mice

2021 ◽  
Author(s):  
Louisa Yeung ◽  
Timothy A Gottschalk ◽  
Pam Hall ◽  
Evelyn Tsantikos ◽  
Rebecca H Gallagher ◽  
...  
Keyword(s):  
Lymphocyte Trafficking ◽  
Systemic Autoimmunity ◽  
Deficient Mice

scholarly journals Enforced Expression of Bcl-2 Partially Restores Cell Numbers but Not Functions of TCRγδ Intestinal Intraepithelial T Lymphocytes in IL-15-Deficient Mice

2007 ◽  
Vol 178 (2) ◽  
pp. 757-764 ◽  
Author(s):  
Kenji Nakazato ◽  
Hisakata Yamada ◽  
Toshiki Yajima ◽  
Yoshiko Kagimoto ◽  
Hiroyuki Kuwano ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Cell Numbers ◽  
Deficient Mice

scholarly journals Egr2 and Egr3 in regulatory T cells cooperatively control systemic autoimmunity through Ltbp3-mediated TGF-β3 production

2016 ◽  
Vol 113 (50) ◽  
pp. E8131-E8140 ◽  
Author(s):  
Kaoru Morita ◽  
Tomohisa Okamura ◽  
Mariko Inoue ◽  
Toshihiko Komai ◽  
Shuzo Teruya ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Lupus Erythematosus ◽  
Mice Model ◽  
Mild Phenotype ◽  
Humoral Immune ◽  
Germinal Center Reaction ◽  
Systemic Autoimmunity ◽  
Deficient Mice

Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease characterized by multiorgan inflammation induced by autoantibodies. Early growth response gene 2 (Egr2), a transcription factor essential for T-cell anergy induction, controls systemic autoimmunity in mice and humans. We have previously identified a subpopulation of CD4+ regulatory T cells, CD4+CD25−LAG3+ cells, that characteristically express both Egr2 and LAG3 and control mice model of lupus via TGF-β3 production. However, due to the mild phenotype of lymphocyte-specific Egr2-deficient mice, the presence of an additional regulator has been speculated. Here, we show that Egr2 and Egr3 expressed in T cells cooperatively prevent humoral immune responses by supporting TGF-β3 secretion. T cell-specific Egr2/Egr3 double-deficient (Egr2/3DKO) mice spontaneously developed an early onset lupus-like disease that was more severe than in T cell-specific Egr2-deficient mice. In accordance with the observation that CD4+CD25−LAG3+ cells from Egr2/3DKO mice completely lost the capacity to produce TGF-β3, the excessive germinal center reaction in Egr2/3DKO mice was suppressed by the adoptive transfer of WT CD4+CD25−LAG3+ cells or treatment with a TGF-β3–expressing vector. Intriguingly, latent TGF-β binding protein (Ltbp)3 expression maintained by Egr2 and Egr3 was required for TGF-β3 production from CD4+CD25−LAG3+ cells. Because Egr2 and Egr3 did not demonstrate cell intrinsic suppression of the development of follicular helper T cells, Egr2- and Egr3-dependent TGF-β3 production by CD4+CD25−LAG3+ cells is critical for controlling excessive B-cell responses. The unique attributes of Egr2/Egr3 in T cells may provide an opportunity for developing novel therapeutics for autoantibody-mediated diseases including SLE.

scholarly journals Tumor-derived extracellular vesicles regulate tumor-infiltrating regulatory T cells via the inhibitory immunoreceptor CD300a

2020 ◽  
Author(s):  
Yuta Nakazawa ◽  
Kazumasa Kanemaru ◽  
Chigusa Nakahashi-Oda ◽  
Akira Shibuya
Keyword(s):  
Dendritic Cells ◽  
Treg Cell ◽  
Cell Activation ◽  
Extracellular Vesicle ◽  
Treg Cells ◽  
Wild Type ◽  
Cell Numbers ◽  
Tumor Microenvironments ◽  
Deficient Mice

AbstractAlthough tumor-infiltrating regulatory T (Treg) cells play a pivotal role in tumor immunity, how Treg cell activation are regulated in tumor microenvironments remains unclear. Here, we found that mice deficient in the inhibitory immunoreceptor CD300a on their dendritic cells (DCs) have increased numbers of Treg cells in tumors and greater tumor growth compared with wild-type mice after transplantation of B16 melanoma. Pharmacological impairment of extracellular vesicle (EV) release decreased Treg cell numbers in CD300a-deficient mice. Coculture of DCs with tumor-derived EV (TEV) induced the internalization of CD300a and the incorporation of EVs into endosomes, in which CD300a inhibited TEV-mediated TLR3-TRIF signaling for activation of the IFN-β-Treg cells axis. We also show that higher expression of CD300A was associated with decreased tumor-infiltrating Treg cells and longer survival time in patients with melanoma. Our findings reveal the role of TEV and CD300a on DCs in Treg cell activation in the tumor microenvironment.

scholarly journals Deficiencies in progenitor cells of multiple hematopoietic lineages and defective megakaryocytopoiesis in mice lacking the thrombopoietic receptor c-Mpl

Blood ◽  
1996 ◽  
Vol 87 (6) ◽  
pp. 2162-2170 ◽  
Author(s):  
WS Alexander ◽  
AW Roberts ◽  
NA Nicola ◽  
R Li ◽  
D Metcalf
Keyword(s):  
Progenitor Cells ◽  
Progenitor Cell ◽  
Specific Binding ◽  
Hematopoietic Progenitor Cell ◽  
Spleen Cells ◽  
Critical Function ◽  
Cell Numbers ◽  
Specific Binding Sites ◽  
Progenitor Cell Proliferation ◽  
Deficient Mice

Mice with a null mutation in the thrombopoietin (TPO) receptor c-Mpl were generated by gene targeting. c-mpl-deficient mice developed normally but were deficient in megakaryocytes and severely thrombocytopenic. The hematocrit and numbers of mature circulating leukocytes were normal in mpl-/- mice, as was the distribution of morphologically identifiable precursors in hematopoietic tissues. Bone marrow and spleen cells of adult mpl-/- mice lacked specific binding sites for TPO, were unresponsive to TPO in culture, and displayed a marked deficiency in progenitor cells with megakaryocytic potential. Significantly, total hematopoietic progenitor cell numbers were also reduced in mpl-/- mice including multipotential, blast cell, and committed progenitors of multiple lineages. The megakaryocyte deficiency was evident as early as 14 days of gestation in mpl- deficient mice, although reductions in progenitor cell numbers arose only later in development. The data suggest that the critical function of c-Mpl signalling in megakaryocytopoiesis is in maintenance of mature megakaryocyte numbers through control of progenitor cell proliferation and maturation. Moreover, our results also imply an important role for TPO and c-Mpl in the production of primitive pluripotent progenitor cells as well as progenitor cells committed to nonmegakaryocytic lineages.

Prion protein-deficient mice exhibit decreased CD4 T and LTi cell numbers and impaired spleen structure

Immunobiology ◽  
2016 ◽  
Vol 221 (1) ◽  
pp. 94-102 ◽  
Author(s):  
Soochan Kim ◽  
Sinsuk Han ◽  
Ye Eun Lee ◽  
Woong-Jae Jung ◽  
Hyung Soo Lee ◽  
...  
Keyword(s):  
Prion Protein ◽  
Cell Numbers ◽  
Deficient Mice

scholarly journals Jak3 Selectively Regulates Bax and Bcl-2 Expression To Promote T-Cell Development

2001 ◽  
Vol 21 (2) ◽  
pp. 678-689 ◽  
Author(s):  
Renren Wen ◽  
Demin Wang ◽  
Catriona McKay ◽  
Kevin D. Bunting ◽  
Jean-Christophe Marine ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
T Cell Development ◽  
Cell Development ◽  
Lymphoid Cells ◽  
Wild Type ◽  
Cell Numbers ◽  
Deficient Mice ◽  
T Lymphopoiesis

ABSTRACT Jak3-deficient mice display vastly reduced numbers of lymphoid cells. Thymocytes and peripheral T cells from Jak3-deficient mice have a high apoptotic index, suggesting that Jak3 provides survival signals. Here we report that Jak3 regulates T lymphopoiesis at least in part through its selective regulation of Bax and Bcl-2. Jak3-deficient thymocytes express elevated levels of Bax and reduced levels of Bcl-2 relative to those in wild-type littermates. Notably, up-regulation of Bax in Jak3-deficient T cells is physiologically relevant, as Jak3 Bax double-null mice have marked increases in thymocyte and peripheral T-cell numbers. Rescue of T lymphopoiesis by Bax loss was selective, as mice deficient in Jak3 plus p53 or in Jak3 plus Fas remained lymphopenic. However, Bax loss failed to restore proper ratios of peripheral CD4/CD8 T cells, which are abnormally high in Jak3-null mice. Transplantation into Jak3-deficient mice of Jak3-null bone marrow transduced with a Bcl-2-expressing retrovirus also improved peripheral T-cell numbers and restored the ratio of peripheral CD4/CD8 T cells to wild-type levels. The data support the concepts that Jak kinases regulate cell survival through their selective and cell context-dependent regulation of pro- and antiapoptotic Bcl-2 family proteins and that Bax and Bcl-2 play distinct roles in T-cell development.

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