scholarly journals Enhanced Interleukin (IL)-13 Responses in Mice Lacking IL-13 Receptor α 2

2003 ◽  
Vol 197 (6) ◽  
pp. 703-709 ◽  
Author(s):  
Nancy Wood ◽  
Matthew J. Whitters ◽  
Bruce A. Jacobson ◽  
JoAnn Witek ◽  
Joseph P. Sypek ◽  
...  
Keyword(s):  
Immune Responses ◽  
Immunoglobulin E ◽  
Interferon Γ ◽  
Wild Type ◽  
Functional Importance ◽  
Bone Marrow Macrophage ◽  
Tissue Macrophage ◽  
High Affinity Receptor ◽  
Affinity Receptor ◽  
Deficient Mice

Interleukin (IL)-13 has recently been shown to play important and unique roles in asthma, parasite immunity, and tumor recurrence. At least two distinct receptor components, IL-4 receptor (R)α and IL-13Rα1, mediate the diverse actions of IL-13. We have recently described an additional high affinity receptor for IL-13, IL-13Rα2, whose function in IL-13 signaling is unknown. To better appreciate the functional importance of IL-13Rα2, mice deficient in IL-13Rα2 were generated by gene targeting. Serum immunoglobulin E levels were increased in IL-13Rα2−/− mice despite the fact that serum IL-13 was absent and immune interferon γ production increased compared with wild-type mice. IL-13Rα2–deficient mice display increased bone marrow macrophage progenitor frequency and decreased tissue macrophage nitric oxide and IL-12 production in response to lipopolysaccharide. These results are consistent with a phenotype of enhanced IL-13 responsiveness and demonstrate a role for endogenous IL-13 and IL-13Rα2 in regulating immune responses in wild-type mice.

scholarly journals Sensitivity of hippocampal 5-HT1A receptors to mild stress in BDNF-deficient mice

2013 ◽  
Vol 16 (3) ◽  
pp. 631-645 ◽  
Author(s):  
Teresa F. Burke ◽  
Tushar Advani ◽  
Megumi Adachi ◽  
Lisa M. Monteggia ◽  
Julie G. Hensler
Keyword(s):  
Mild Stress ◽  
Emotional States ◽  
Receptor Function ◽  
Wild Type ◽  
Bdnf Expression ◽  
Handling Stress ◽  
Gtpγs Binding ◽  
High Affinity Receptor ◽  
Affinity Receptor ◽  
Deficient Mice

Abstract Serotonin 1A (5-HT1A) receptors in brain play an important role in cognitive and integrative functions, as well as emotional states. Decreased brain-derived neurotrophic factor (BDNF) expression and/or function, particularly in hippocampus, are implicated in the pathophysiology of stress-related disorders such as major depression. BDNF+/− mice are more vulnerable to stress than wild-type mice, exhibiting behavioural despair after mild handling stress. We examined the effect of mild handling stress on 5-HT1A receptor function, as measured by 8-OH-DPAT stimulated [35S]GTPγS binding, in BDNF+/− mice and mice with a forebrain-specific reduction in BDNF (embryonic BDNF inducible knockout mice). Our data show a remarkable sensitivity of hippocampal 5-HT1A receptors to mild stress and a deficiency in BDNF. Other 5-HT1A receptor populations, specifically in frontal cortex and dorsal raphe, were resistant to the combined detrimental effects of mild stress and reductions in BDNF expression. Decreases in hippocampal 5-HT1A receptor function induced by mild stress in BDNF-deficient mice were prevented by administration of the selective serotonin reuptake inhibitor fluoxetine, which increased activation of TrkB, the high affinity receptor for BDNF, in wild-type and BDNF+/− mice. In hippocampal cultures, BDNF increased the capacity of 5-HT1A receptors to activate G proteins, an effect eliminated by the knockout of TrkB, confirming TrkB activation increases 5-HT1A receptor function. The mechanisms underlying the sensitivity of hippocampal 5-HT1A receptors to mild stress and decreased BDNF expression remain to be elucidated and may have important implications for the emotional and cognitive impairments associated with stress-related mental illness.

scholarly journals A role for CD9 molecules in T cell activation.

1996 ◽  
Vol 184 (2) ◽  
pp. 753-758 ◽  
Author(s):  
X G Tai ◽  
Y Yashiro ◽  
R Abe ◽  
K Toyooka ◽  
C R Wood ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
T Cell Activation ◽  
Cell Activation ◽  
Expression Cloning ◽  
Wild Type ◽  
Almost All ◽  
Antigen Presenting ◽  
Deficient Mice

Costimulation mediated by the CD28 molecule plays an important role in optimal activation of T cells. However, CD28-deficient mice can mount effective T cell-dependent immune responses, suggesting the existence of other costimulatory systems. In a search for other costimulatory molecules on T cells, we have developed a monoclonal antibody (mAb) that can costimulate T cells in the absence of antigen-presenting cells (APC). The molecule recognized by this mAb, 9D3, was found to be expressed on almost all mature T cells and to be a protein of approximately 24 kD molecular mass. By expression cloning, this molecule was identified as CD9, 9D3 (anti-CD9) synergized with suboptimal doses of anti-CD3 mAb in inducing proliferation by virgin T cells. Costimulation was induced by independent ligation of CD3 and CD9, suggesting that colocalization of these two molecules is not required for T cell activation. The costimulation by anti-CD9 was as potent as that by anti-CD28. Moreover, anti-CD9 costimulated in a CD28-independent way because anti-CD9 equally costimulated T cells from the CD28-deficient as well as wild-type mice. Thus, these results indicate that CD9 serves as a molecule on T cells that can deliver a potent CD28-independent costimulatory signal.

scholarly journals The Role of Vitamin D and Vitamin D Receptor in Immunity toLeishmania majorInfection

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
James P. Whitcomb ◽  
Mary DeAgostino ◽  
Mark Ballentine ◽  
Jun Fu ◽  
Martin Tenniswood ◽  
...  
Keyword(s):  
Vitamin D ◽  
Immune Responses ◽  
Vitamin D Receptor ◽  
Leishmania Major ◽  
Active Form ◽  
Wild Type ◽  
Vitamin D Signaling ◽  
Deficient Mice ◽  
Th 1

Vitamin D signaling modulates a variety of immune responses. Here, we assessed the role of vitamin D in immunity to experimental leishmaniasis infection in vitamin D receptor-deficient mice (VDRKO). We observed that VDRKO mice on a genetically resistant background have decreasedLeishmania major-induced lesion development compared to wild-type (WT) mice; additionally, parasite loads in infected dermis were significantly lower at the height of infection. Enzymatic depletion of the active form of vitamin D mimics the ablation of VDR resulting in an increased resistance toL. major. Conversely, VDRKO or vitamin D-deficient mice on the susceptible Th2-biased background had no change in susceptibility. These studies indicate vitamin D deficiency, either through the ablation of VDR or elimination of its ligand, 1,25D3, leads to an increase resistance toL. majorinfection but only in a host that is predisposed for Th-1 immune responses.

The High Affinity Receptor for Immunoglobulin E: New Developments

1989 ◽  
pp. 716-723 ◽  
Author(s):  
J.-P. Kinet ◽  
H. Metzger ◽  
G. Alber ◽  
U. Blank ◽  
K. Huppi ◽  
...  
Keyword(s):  
Immunoglobulin E ◽  
New Developments ◽  
High Affinity ◽  
High Affinity Receptor ◽  
Affinity Receptor

Intraepithelial lymphocyte-derived interferon-γ evokes enterocyte apoptosis with parenteral nutrition in mice

2003 ◽  
Vol 284 (4) ◽  
pp. G629-G637 ◽  
Author(s):  
Hua Yang ◽  
Yongyi Fan ◽  
Daniel H. Teitelbaum
Keyword(s):  
Parenteral Nutrition ◽  
Fas Ligand ◽  
Interferon Γ ◽  
Intraepithelial Lymphocyte ◽  
Wild Type ◽  
Enterocyte Apoptosis ◽  
Resultant Increase ◽  
Ifn Γ ◽  
Fas L ◽  
Deficient Mice

Total parenteral nutrition (TPN) results in an increase in intraepithelial lymphocyte (IEL)-derived interferon-γ (IFN-γ) expression as well as an increase in epithelial cell (EC) apoptosis. This study examined the role that IEL-derived IFN-γ has in the increase in EC apoptosis. Mice received either TPN or oral feedings for 7 days. Small bowel EC apoptosis significantly rose in mice receiving TPN. The administration of TPN also significantly increased IEL-derived IFN-γ and Fas ligand (FasL) expression. EC apoptosis in IFN-γ knockout (IFNKO) mice that received TPN was significantly lower than in wild-type TPN mice. Sensitivity of EC to Fas-mediated apoptosis in IFNKO mice was significantly lower than in wild-type TPN mice. Apoptosis in Fas-deficient and FasL-deficient mice that received TPN was significantly lower than in wild-type mice that received TPN. The TPN-induced increase in IFN-γ expression appears to result in an increase in Fas-L expression and EC sensitivity to Fas, with a resultant increase in EC apoptosis. This may well be one of the mediators of increased EC apoptosis observed with TPN administration.

scholarly journals Requirement for the Chemokine Receptor Ccr6 in Allergic Pulmonary Inflammation

2001 ◽  
Vol 194 (4) ◽  
pp. 551-556 ◽  
Author(s):  
Nicholas W. Lukacs ◽  
Dina M. Prosser ◽  
Maria Wiekowski ◽  
Sergio A. Lira ◽  
Donald N. Cook
Keyword(s):  
Cytokine Production ◽  
Immunoglobulin E ◽  
Pulmonary Inflammation ◽  
Allergen Challenge ◽  
Serum Levels ◽  
Airway Hyperreactivity ◽  
Wild Type ◽  
Interleukin 5 ◽  
Helper Cell Type ◽  
Deficient Mice

Allergic asthmatic responses in the airway are associated with airway hyperreactivity, eosinophil accumulation in the lung, and cytokine production by allergen-specific, T helper cell type 2 (Th2) lymphocytes. Here, we show that in a cockroach antigen (CA) model of allergic pulmonary inflammation, the chemokine macrophage inflammatory protein (MIP)-3α is expressed in the lung within hours of allergen challenge. To determine the biologic relevance of this expression, mice lacking CCR6, the only known receptor for MIP-3α, were studied for their response to CA. CCR6-deficient mice were immunized to the same extent as their wild-type counterparts, as judged by cytokine production in antigen-challenged lymphocytes. However, compared with CA-challenged wild-type mice, challenged CCR6-deficient mice had reduced airway resistance, fewer eosinophils around the airway, lower levels of interleukin 5 in the lung, and reduced serum levels of immunoglobulin E. Together, these data demonstrate that MIP-3α and CCR6 function in allergic pulmonary responses and suggest that these molecules might represent novel therapeutic targets for treatment of asthma.

Crystal structure of a complex between interferon-γ and its soluble high-affinity receptor

Nature ◽  
1995 ◽  
Vol 376 (6537) ◽  
pp. 230-235 ◽  
Author(s):  
Mark R. Walter ◽  
William T. Windsor ◽  
Tattanahalli L. Nagabhushan ◽  
Daniel J. Lundell ◽  
Charles A. Lunn ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Interferon Γ ◽  
High Affinity ◽  
High Affinity Receptor ◽  
Affinity Receptor
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