scholarly journals Expression of Immunoregulatory Molecules by Thyrocytes Protects Nonobese Diabetic-H2h4 Mice from Developing Autoimmune Thyroiditis

Endocrinology ◽  
2008 ◽  
Vol 150 (3) ◽  
pp. 1545-1551 ◽  
Author(s):  
Mami Nakahara ◽  
Yuji Nagayama ◽  
Ohki Saitoh ◽  
Rintaro Sogawa ◽  
Shigenobu Tone ◽  
...  
Keyword(s):  
Autoimmune Diseases ◽  
Adenovirus Vector ◽  
Target Tissue ◽  
Tissue Destruction ◽  
Indoleamine 2 ◽  
Nonobese Diabetic ◽  
Autoimmune Attack ◽  
Thyroid Glands ◽  
Organ Specific

One approach to prevent tissue destruction by autoimmune attack in organ-specific autoimmune diseases is to protect the target tissue from autoimmune reaction, regardless of its persistent activity. To provide proof-of-principle for the feasibility of this approach, the immunoregulatory molecules, TNF-related apoptosis-inducing ligand (TRAIL) and indoleamine 2, 3-dioxygenase, were expressed in the thyroid glands using adenovirus vector in nonobese diabetic-H2h4 mice that spontaneously develop thyroiditis. Mice were anesthetized, and the thyroid glands were exposed by neck dissection, followed by in situ infection with adenovirus vector (5 × 1010 particles per mouse) twice or thrice, starting 1 d or 4 wk before mice were supplied with sodium iodine (NaI) water. After 8 wk NaI provision, the extent of thyroiditis, serum titers of antithyroglobulin antibodies, and cytokine expression in the spleen were examined. In situ infection of adenovirus expressing TRAIL or indoleamine 2, 3-dioxygenase, but not green fluorescent protein, significantly suppressed thyroiditis scores. However, antithyroglobulin antibody titers and expression levels of cytokines (interferon-γ and IL-4) in the spleen remained unaltered. Importantly, adenovirus infection 4 wk after NaI provision was also effective at suppressing thyroiditis. The suppressive effect of TRAIL appears to be mediated at least partly by accumulation of CD4+Foxp3+ regulatory T cells into the thyroid glands. Thus, localized expression of immunoregulatory molecules efficiently protected the thyroid glands from autoimmune attack without changing the systemic autoimmunity in nonobese diabetic-H2h4 mice. This kind of immunological intervention, although it does not suppress autoimmune reactivity, may have a potential for treating organ-specific autoimmune diseases. The feasibility of in situ expression of the immuno-regulatory molecules to prevent tissue destruction by autoimmune attack in organ-specific autoimmune diseases is discussed.

scholarly journals The effect of regulatory T-cell depletion on the spectrum of organ-specific autoimmune diseases in nonobese diabetic mice at different ages

Autoimmunity ◽  
2011 ◽  
Vol 44 (6) ◽  
pp. 504-510 ◽  
Author(s):  
Mami Nakahara ◽  
Yuji Nagayama ◽  
Tatsuki Ichikawa ◽  
Liping Yu ◽  
George S. Eisenbarth ◽  
...  
Keyword(s):  
T Cell ◽  
Autoimmune Diseases ◽  
Regulatory T Cell ◽  
Cell Depletion ◽  
Diabetic Mice ◽  
T Cell Depletion ◽  
Nonobese Diabetic ◽  
Different Ages ◽  
Organ Specific ◽  
Nonobese Diabetic Mice

Infants Diagnosed with Athyreosis on Scintigraphy May Have a Gland Present on Ultrasound and Have Transient Congenital Hypothyroidism

2021 ◽  
pp. 1-8
Author(s):  
Niamh McGrath ◽  
Colin Patrick Hawkes ◽  
Stephanie Ryan ◽  
Philip Mayne ◽  
Nuala Murphy
Keyword(s):  
Thyroid Gland ◽  
Congenital Hypothyroidism ◽  
Thyroid Tissue ◽  
Thyroid Stimulating Hormone ◽  
Thyroid Ultrasound ◽  
Free T4 ◽  
Median Serum ◽  
Thyroid Glands ◽  
Rule Out

Scintigraphy using technetium-99m (<sup>99m</sup>Tc) is the gold standard for imaging the thyroid gland in infants with congenital hypothyroidism (CHT) and is the most reliable method of diagnosing an ectopic thyroid gland. One of the limitations of scintigraphy is the possibility that no uptake is detected despite the presence of thyroid tissue, leading to the spurious diagnosis of athyreosis. Thyroid ultrasound is a useful adjunct to detect thyroid tissue in the absence of <sup>99m</sup>Tc uptake. <b><i>Aims:</i></b> We aimed to describe the incidence of sonographically detectable in situ thyroid glands in infants scintigraphically diagnosed with athyreosis using <sup>99m</sup>Tc and to describe the clinical characteristics and natural history in these infants. <b><i>Methods:</i></b> The newborn screening records of all infants diagnosed with CHT between 2007 and 2016 were reviewed. Those diagnosed with CHT and athyreosis confirmed on scintigraphy were invited to attend a thyroid ultrasound. <b><i>Results:</i></b> Of the 488 infants diagnosed with CHT during the study period, 18/73 (24.6%) infants with absent uptake on scintigraphy had thyroid tissue visualised on ultrasound (3 hypoplastic thyroid glands and 15 eutopic glands). The median serum thyroid-stimulating hormone (TSH) concentration at diagnosis was significantly lower than that in infants with confirmed athyreosis (no gland on ultrasound and no uptake on scintigraphy) (74 vs. 270 mU/L), and median free T4 concentration at diagnosis was higher (11.9 vs. 3.9 pmol/L). Six of 10 (60%) infants with no uptake on scintigraphy but a eutopic gland on ultrasound had transient CHT. <b><i>Conclusion:</i></b> Absent uptake on scintigraphy in infants with CHT does not rule out a eutopic gland, especially in infants with less elevated TSH concentrations. Clinically, adding thyroid ultrasound to the diagnostic evaluation of infants who have athyreosis on scintigraphy may avoid committing some infants with presumed athyreosis to lifelong levothyroxine treatment.

The role of IL-12 in the induction of organ-specific autoimmune diseases

1995 ◽  
Vol 16 (8) ◽  
pp. 383-386 ◽  
Author(s):  
Sylvie Trembleau ◽  
Luciano Adorini ◽  
Tieno Germann ◽  
Maurice K. Gately
Keyword(s):  
Autoimmune Diseases ◽  
Organ Specific

Autoantibodies typical of non-organ-specific autoimmune diseases in HIV-seropositive patients

AIDS ◽  
1992 ◽  
Vol 6 (9) ◽  
pp. 933-942 ◽  
Author(s):  
Sylviane Muller ◽  
Pascale Richalet ◽  
Anne Laurent-Crawford ◽  
Samira Barakat ◽  
Yves Rivière ◽  
...  
Keyword(s):  
Autoimmune Diseases ◽  
Organ Specific ◽  
Hiv Seropositive

scholarly journals Defective Suppressor Function of Human CD4+ CD25+ Regulatory T Cells in Autoimmune Polyglandular Syndrome Type II

2004 ◽  
Vol 199 (9) ◽  
pp. 1285-1291 ◽  
Author(s):  
Martin A. Kriegel ◽  
Tobias Lohmann ◽  
Christoph Gabler ◽  
Norbert Blank ◽  
Joachim R. Kalden ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Autoimmune Diseases ◽  
Type I ◽  
Type Ii ◽  
Central Tolerance ◽  
Autoimmune Polyglandular Syndrome ◽  
Healthy Donors ◽  
Organ Specific ◽  
Autoimmune Polyglandular Syndrome Type

In autoimmune polyglandular syndromes (APS), several organ-specific autoimmune diseases are clustered. Although APS type I is caused by loss of central tolerance, the etiology of APS type II (APS-II) is currently unknown. However, in several murine models, depletion of CD4+ CD25+ regulatory T cells (Tregs) causes a syndrome resembling human APS-II with multiple endocrinopathies. Therefore, we hypothesized that loss of active suppression in the periphery could be a hallmark of this syndrome. Tregs from peripheral blood of APS-II, control patients with single autoimmune endocrinopathies, and normal healthy donors showed no differences in quantity (except for patients with isolated autoimmune diseases), in functionally important surface markers, or in apoptosis induced by growth factor withdrawal. Strikingly, APS-II Tregs were defective in their suppressive capacity. The defect was persistent and not due to responder cell resistance. These data provide novel insights into the pathogenesis of APS-II and possibly human autoimmunity in general.

Differentiation of allantoic endoderm implanted into the presumptive digestive area in avian embryos. A study with organ-specific antigens

Development ◽  
1984 ◽  
Vol 80 (1) ◽  
pp. 137-153
Author(s):  
Sadao Yasugi
Keyword(s):  
Digestive Tract ◽  
Intestinal Epithelium ◽  
Digestive Organ ◽  
Chick Embryos ◽  
Avian Embryos ◽  
Digestive Organs ◽  
Organ Specific ◽  
Specific Antigens

Quail allantoic endoderm was implanted into the presumptive digestive-tract area of chick embryos, and the differentiation of the endoderm was examined morphologically and immunocytochemically with antisera against pepsinogens and sucrase. The allantoic endoderm was incorporated into the host digestive organs. It often became continuous with the host endoderm and formed a chimaeric digestive-tract epithelium. It differentiated morphologically into the epithelium of the digestive organ into which it was incorporated, showing the morphological inductive ability in situ of the digestive-tract mesenchyme against the allantoic endoderm. However, the allantoic endoderm did not produce pepsinogens even when it was incorporated into the host proventricular mesenchyme and formed well-developed proventricular glands. This result indicates that the heterotypic morphogenesis of the allantoic endoderm is not necessarily accompanied by the heterotypic cytodifferentiation. In contrast, the anti-sucrase antiserum-reactive cells often differentiated in the allantoic endoderm incorporated into not only the intestine but also other organs. This confirmed our previous observation that the allantoic endoderm has a tendency to differentiate into the intestinal epithelium in the heterologous environment.

scholarly journals Cytokine expression in the duodenal mucosa of patients with visceral leishmaniasis

2010 ◽  
Vol 43 (4) ◽  
pp. 393-395 ◽  
Author(s):  
Kleber Giovanni Luz ◽  
Felipe Francisco Tuon ◽  
Maria Irma Seixas Duarte ◽  
Guilherme Mariz Maia ◽  
Paulo Matos ◽  
...  
Keyword(s):  
Immune Response ◽  
Gastrointestinal Tract ◽  
Visceral Leishmaniasis ◽  
Intestinal Bacteria ◽  
Duodenal Mucosa ◽  
Control Group ◽  
Tnf Α ◽  
Organ Specific ◽  
Ifn Γ

INTRODUCTION: Visceral leishmaniasis (VL) is a neglected tropical disease with a complex immune response in different organs. This pattern of organ-specific immune response has never been evaluated in the gastrointestinal tract. The aim of this study was to determine the in situ immune response in duodenal biopsies on patients with VL. METHODS: A case-control study was conducted on 13 patients with VL in comparison with nine controls. The immune response was evaluated using immunohistochemistry, for CD4, CD8, CD68, IL-4, IFN-γ, TNF-α and IL-10. Histological findings from the villi, crypts and inflammatory process were analyzed. RESULTS: All the cases of VL presented Leishmania antigens. No antigen was detected in the control group. The villus size was greater in the VL patients (p < 0.05). CD68 (macrophages) and CD4 levels were higher in the VL patients (p < 0.05). No differences in the expression of CD8, TNF-α, IL-10 or IL-4 were demonstrated. The number of cells expressing IFN-γ was lower in the VL patients (p < 0.05). CONCLUSIONS: Low levels of cytokines were found in the gastrointestinal tract of patients with VL. This pattern was not found in other organs affected by the disease. Immunotolerance of this tissue against Leishmania could explain these findings, as occurs with intestinal bacteria.

In situ activation of mouse alveolar macrophages by aerosolized liposomal IFN-gamma and muramyl tripeptide

1996 ◽  
Vol 270 (3) ◽  
pp. L429-L434 ◽  
Author(s):  
P. Goldbach ◽  
S. Dumont ◽  
R. Kessler ◽  
P. Poindron ◽  
A. Stamm
Keyword(s):  
Alveolar Macrophages ◽  
Peritoneal Macrophages ◽  
Target Cells ◽  
Tumoricidal Activity ◽  
Ifn Gamma ◽  
In Situ Activation ◽  
Organ Specific ◽  
Thawing Procedure

Interferon-gamma (IFN-gamma) was entrapped with an efficiency of 30-40% in muramyl tripeptide-containing liposomes by a freeze-thawing procedure. A microcytotoxicity assay was developed to measure the tumoricidal activity of mouse alveolar macrophages (AM) against tumoral target cells with a colorimetric viability test. Free IFN-gamma and liposomal muramyl tripeptide phosphatidylethanolamine (MTP-PE) were found to be only slightly effective to activate in vitro AM, whereas encapsulation of both INF-gamma and MTP-PE within the same liposomes produced higher activation of AM. Aerosolized IFN-gamma and liposomal immunomodulators enhanced antitumor properties of AM recovered in mice 24 h postinhalation. Whereas free IFN-gamma also induced a substantial activation of peritoneal macrophages, liposomal encapsulation significantly reduced the systemic activity of inhaled immunomodulators. This approach provides a useful model for the compartmentalized organ-specific activation of AM in mice.

Expression of vascular permeability factor/vascular endothelial growth factor in normal rat tissues

1993 ◽  
Vol 264 (4) ◽  
pp. C995-C1002 ◽  
Author(s):  
W. T. Monacci ◽  
M. J. Merrill ◽  
E. H. Oldfield
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
In Situ Hybridization ◽  
Rat Tissues ◽  
Vascular Endothelial ◽  
Vascular Permeability Factor ◽  
Organ Specific ◽  
Normal Rat ◽  
Endothelial Growth Factor ◽  
The Brain

Vascular permeability factor (VPF)/vascular endothelial growth factor (VEGF) is a approximately 43-kDa secreted protein that has been shown in bioassays to induce endothelial proliferation, angiogenesis, and capillary hyperpermeability. VPF has been suggested to play an important role in the physiology of normal vasculature. To further elucidate the natural functions of VPF in vivo, the expression of VPF in normal tissues was examined using Northern blot analysis and in situ hybridization histochemistry. VPF mRNA is expressed in the brain, kidney, liver, lung, and spleen of the healthy adult rat. On Northern blots, the relative abundance of VPF mRNA observed in these tissues was highest in the lung and lowest in the spleen. As determined by in situ hybridization, the patterns of VPF expression are organ specific. Hybridization of an antisense VPF probe was concentrated in the cerebellar granule cell layer of the brain and in the glomeruli and tubules of the kidney. In the liver and lung, intense hybridization was observed homogeneously throughout both tissues, demonstrating that VPF mRNA is present in virtually every hepatocyte and pulmonary alveolar cell. Hybridization to the spleen was weaker and more diffuse. The widespread expression and organ-specific distribution of VPF mRNA in normal rat tissues supports the suggestion of an extensive role for this factor in the physiology of normal vasculature.

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