scholarly journals Lymphopenia, Lymphopenia-Induced Proliferation, and Autoimmunity

2021 ◽  
Vol 22 (8) ◽  
pp. 4152
Author(s):  
Ting-Ting Sheu ◽  
Bor-Luen Chiang
Keyword(s):  
The Elderly ◽  
Treg Cells ◽  
Causative Role ◽  
Loss Of Control ◽  
Physiological Conditions ◽  
Autoimmune Conditions ◽  
Function Number ◽  
Lymphocyte Number

Immune homeostasis is a tightly regulated system that is critical for defense against invasion by foreign pathogens and protection from self-reactivity for the survival of an individual. How the defects in this system might result in autoimmunity is discussed in this review. Reduced lymphocyte number, termed lymphopenia, can mediate lymphopenia-induced proliferation (LIP) to maintain peripheral lymphocyte numbers. LIP not only occurs in normal physiological conditions but also correlates with autoimmunity. Of note, lymphopenia is also a typical marker of immune aging, consistent with the fact that not only the autoimmunity increases in the elderly, but also autoimmune diseases (ADs) show characteristics of immune aging. Here, we discuss the types and rates of LIP in normal and autoimmune conditions, as well as the coronavirus disease 2019 in the context of LIP. Importantly, although the causative role of LIP has been demonstrated in the development of type 1 diabetes and rheumatoid arthritis, a two-hit model has suggested that the factors other than lymphopenia are required to mediate the loss of control over homeostasis to result in ADs. Interestingly, these factors may be, if not totally, related to the function/number of regulatory T cells which are key modulators to protect from self-reactivity. In this review, we summarize the important roles of lymphopenia/LIP and the Treg cells in various autoimmune conditions, thereby highlighting them as key therapeutic targets for autoimmunity treatments.

scholarly journals IL-10 Deficiency Accelerates Type 1 Diabetes Development via Modulation of Innate and Adaptive Immune Cells and Gut Microbiota in BDC2.5 NOD Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Juan Huang ◽  
Qiyuan Tan ◽  
Ningwen Tai ◽  
James Alexander Pearson ◽  
Yangyang Li ◽  
...  
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
T Cell ◽  
Gut Microbiota ◽  
Spontaneous Diabetes ◽  
Nod Mice ◽  
Treg Cells ◽  
Diabetes Development

Type 1 diabetes is an autoimmune disease caused by T cell-mediated destruction of insulin-producing β cells. BDC2.5 T cells in BDC2.5 CD4+ T cell receptor transgenic Non-Obese Diabetic (NOD) mice (BDC2.5+ NOD mice) can abruptly invade the pancreatic islets resulting in severe insulitis that progresses rapidly but rarely leads to spontaneous diabetes. This prevention of diabetes is mediated by T regulatory (Treg) cells in these mice. In this study, we investigated the role of interleukin 10 (IL-10) in the inhibition of diabetes in BDC2.5+ NOD mice by generating Il-10-deficient BDC2.5+ NOD mice (BDC2.5+Il-10-/- NOD mice). Our results showed that BDC2.5+Il-10-/- NOD mice displayed robust and accelerated diabetes development. Il-10 deficiency in BDC2.5+ NOD mice promoted the generation of neutrophils in the bone marrow and increased the proportions of neutrophils in the periphery (blood, spleen, and islets), accompanied by altered intestinal immunity and gut microbiota composition. In vitro studies showed that the gut microbiota from BDC2.5+Il-10-/- NOD mice can expand neutrophil populations. Moreover, in vivo studies demonstrated that the depletion of endogenous gut microbiota by antibiotic treatment decreased the proportion of neutrophils. Although Il-10 deficiency in BDC2.5+ NOD mice had no obvious effects on the proportion and function of Treg cells, it affected the immune response and activation of CD4+ T cells. Moreover, the pathogenicity of CD4+ T cells was much increased, and this significantly accelerated the development of diabetes when these CD4+ T cells were transferred into immune-deficient NOD mice. Our study provides novel insights into the role of IL-10 in the modulation of neutrophils and CD4+ T cells in BDC2.5+ NOD mice, and suggests important crosstalk between gut microbiota and neutrophils in type 1 diabetes development.

scholarly journals Estrogen-Metabolizing Enzymes in Breast Cancers from Women over the Age of 80 Years

2006 ◽  
Vol 91 (2) ◽  
pp. 607-613 ◽  
Author(s):  
Naoko Honma ◽  
Kaiyo Takubo ◽  
Motoji Sawabe ◽  
Tomio Arai ◽  
Futoshi Akiyama ◽  
...  
Keyword(s):  
Normal Tissue ◽  
The Elderly ◽  
Normal Breast ◽  
Specific Pattern ◽  
Steroid Sulfatase ◽  
Mrna Levels ◽  
Breast Cancers ◽  
Metabolizing Enzymes

Context: Aromatase, steroid sulfatase, and 17β-hydroxysteroid dehydrogenase type 1 (HSD-1) peripherally up-regulate, whereas estrogen sulfotransferase (EST) and HSD-2 down-regulate, the synthesis of active and more potent estrogens. These estrogen-metabolizing enzymes (EMEs) are important in postmenopausal breast cancers, but have never been systematically examined in breast cancers of the elderly. Objective and Design: mRNA levels of EMEs in cancerous and normal breast tissues from 39 elderly patients (age, 80–99 yr) were compared with those from 39 controls (age, 37–70 yr) or compared according to estrogen (ER)/progesterone (PR) receptor status. Results: Aromatase levels were higher in cancers of the elderly (EldCa) than in normal tissue of the elderly (P = 0.0008) or cancers of controls (P = 0.0033). In contrast, levels of steroid sulfatase and EST were higher in cancers of controls than normal tissue of controls (P = 0.0046 and P < 0.0001, respectively) or EldCa (P = 0.0001 and P < 0.0001, respectively). Levels of HSD-1 and HSD-2 did not differ significantly between any two of the categories. Among EldCa, HSD-1 levels were higher in ER/PR-positive than in ER/PR-negative carcinomas, whereas EST and HSD-2 exhibited opposite results. Conclusions: The importance of aromatase is relatively increased in EldCa. ER/PR-positive EldCa exhibited a pattern of EMEs more beneficial to the production of estrogen than did ER/PR-negative EldCa. The specific pattern exhibited in EldCa may elucidate the role of EMEs in the absence of ovarian estrogens in the pathogenesis of breast cancer.

scholarly journals Serine 182 on RORγt regulates T helper 17 and regulatory T cell functions to resolve inflammation

2021 ◽  
Author(s):  
Shengyun Ma ◽  
Shefali Patel ◽  
Nicholas Chen ◽  
Parth R Patel ◽  
Benjamin S Cho ◽  
...  
Keyword(s):  
T Cell ◽  
Treg Cells ◽  
Orphan Receptor ◽  
T Helper 17 ◽  
Autoimmune Encephalomyelitis ◽  
Tissue Inflammation ◽  
Cell Functions ◽  
Autoimmune Conditions ◽  
Delayed Recovery

Unresolved inflammation causes tissue damage and contributes to autoimmune conditions. However, the molecules and mechanisms controlling T cell mediated inflammation remain to be fully elucidated. Here, we report an unexpected role of the RAR-Related Orphan Receptor-gamma protein (RORγt) in resolving tissue inflammation. Single-cell RNA-seq (scRNA-seq) revealed that an evolutionarily conserved serine 182 residue on ROR&γt (RORγtS182) is critical for restricting IL-1β-mediated Th17 activities and promoting anti-inflammatory cytokine IL-10 production in RORγt+ Treg cells in inflamed tissues. Phospho-null RORγtS182A knock-in mice experienced delayed recovery and succumbed to exacerbated diseases after dextran sulfate sodium (DSS) induced colitis and experimental autoimmune encephalomyelitis (EAE) challenge. Together, these results highlight the essential role of ROR&γtS182 in resolving T cell mediated tissue inflammation, providing a potential therapeutic target to combat autoimmune diseases.

255-LB: The Role of Th1, Th2, Th17, and Treg Cells in Various Clinical Phases of Type 1 Diabetes

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 255-LB
Author(s):  
BURCIN AYDIN OZGUR ◽  
SUZAN CINAR ◽  
DERYA OZTURK ◽  
ENDER COSKUNPINAR ◽  
ALI OSMAN GUROL ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Treg Cells

Idiopathic bilateral facial palsy: is a causative role of anti-GM1 ganglioside and herpes simplex type 1 possible?

2011 ◽  
Vol 33 (4) ◽  
pp. 951-953 ◽  
Author(s):  
Elena Pretegiani ◽  
Francesca Rosini ◽  
Donatella Donati ◽  
Alessandra Rufa ◽  
Donatella Moschettini ◽  
...  
Keyword(s):  
Herpes Simplex ◽  
Facial Palsy ◽  
Herpes Simplex Type ◽  
Causative Role ◽  
Gm1 Ganglioside

scholarly journals Molecular Examination of Trichomonas vaginalis Infection and Risk of Prostate Cancer in the Biopsy of Patients with Different Prostate Lesions

2021 ◽  
Vol 31 (2) ◽  
Author(s):  
Zeinab Kamarkhani ◽  
Raheleh Rafiei-Sefiddashti ◽  
Leila Haghighi ◽  
Alireza Badirzadeh
Keyword(s):  
Prostate Cancer ◽  
Trichomonas Vaginalis ◽  
Potential Role ◽  
The Elderly ◽  
Diagnostic Techniques ◽  
Causative Role ◽  
Sexually Transmitted ◽  
Polymerase Chain ◽  
Urological Diseases

BACKGROUND፡ Trichomoniasis is a sexually transmitted infectious disease caused by a flagellated protozoa, Trichomonas vaginalis (T.vaginalis) and is often asymptomatic in men. Benign prostatic hyperplasia (BPH) and prostate cancer (PCA) are the most common urological diseases in the elderly. Scientists have proposed various factors which trigger prostate cancer, including sexually transmitted diseases. Thus, this study aimed to evaluate the potential role of T. vaginalis as a risk factor for various prostate lesions such as hyperplasia and prostate cancer.METHODS: A total of 250 paraffin-embedded of different prostate lesion biopsies were analyzed by Polymerase Chain Reaction (PCR) using the beta-tubulin gene for identifying T. vaginalis.RESULT: All 250 pathologic specimens were negative for this parasite by using PCR technique.CONCLUSION: It seems that T. vaginalis may have not had a causative role for different prostate lesions and it seems proposed PCR technique is an insufficient method to find the parasite in paraffin-embedded tissues. Therefore, other diagnostic techniques to identify the parasite in biopsy samples are suggested.

scholarly journals Th17 Cells in Type 1 Diabetes: Role in the Pathogenesis and Regulation by Gut Microbiome

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Yangyang Li ◽  
Yu Liu ◽  
Cong-Qiu Chu
Keyword(s):  
Type 1 Diabetes ◽  
Gut Microbiota ◽  
Th17 Cells ◽  
Current Knowledge ◽  
Treg Cells ◽  
Protective Role ◽  
Islet Autoimmunity ◽  
Genetic And Environmental Factors

Type 1 diabetes (T1D) is an autoimmune disease which is characterized by progressive destruction of insulin producing pancreatic isletβcells. The risk of developing T1D is determined by both genetic and environmental factors. A growing body of evidence supports an important role of T helper type 17 (Th17) cells along with impaired T regulatory (Treg) cells in the development of T1D in animal models and humans. Alteration of gut microbiota has been implicated to be responsible for the imbalance between Th17 and Treg cells. However, there is controversy concerning a pathogenic versus protective role of Th17 cells in murine models of diabetes in the context of influence of gut microbiota. In this review we will summarize current knowledge about Th17 cells and gut microbiota involved in T1D and propose Th17 targeted therapy in children with islet autoimmunity to prevent progression to overt diabetes.

scholarly journals The Interplay between Immune System and Microbiota in Diabetes

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Simona Moffa ◽  
Teresa Mezza ◽  
Chiara M. A. Cefalo ◽  
Francesca Cinti ◽  
Flavia Impronta ◽  
...  
Keyword(s):  
Immune System ◽  
Gut Microbiota ◽  
Metabolic Diseases ◽  
Eating Habits ◽  
Structural Evolution ◽  
Causative Role ◽  
Immune Mediated ◽  
Onset Of Diabetes

Diabetes is not a single and homogeneous disease, but a cluster of metabolic diseases characterized by the common feature of hyperglycemia. The pathogenesis of type 1 diabetes (T1D) and type 2 diabetes (T2D) (and all other intermediate forms of diabetes) involves the immune system, in terms of inflammation and autoimmunity. The past decades have seen an increase in all types of diabetes, accompanied by changes in eating habits and consequently a structural evolution of gut microbiota. It is likely that all these events could be related and that gut microbiota alterations might be involved in the immunomodulation of diabetes. Thus, gut microbiota seems to have a direct, even causative role in mediating connections between the environment, food intake, and chronic disease. As many conditions that increase the risk of diabetes modulate gut microbiota composition, it is likely that immune-mediated reactions, induced by alterations in the composition of the microbiota, can act as facilitators for the onset of diabetes in predisposed subjects. In this review, we summarize recent evidence in the field of gut microbiota and the role of the latter in modulating the immune reactions involved in the pathogenesis of diabetes.

Monogenic Diabetes in a Family with 2 unknown HNF-4A Gene Mutations

2011 ◽  
Vol 120 (02) ◽  
pp. 89-90 ◽  
Author(s):  
M. Motzkau ◽  
P. Meyer ◽  
P.R. Mertens ◽  
S. Klose
Keyword(s):  
Diabetes Mellitus ◽  
Direct Sequencing ◽  
Gene Mutations ◽  
Causative Role ◽  
Glucose Levels ◽  
Mutational Screening ◽  
Glucose Challenge ◽  
Elevated Glucose

AbstractDiabetes mellitus classified as Maturity Onset Diabetes of the Young (MODY) is characterized by autosomal dominant inheritance with insulin secretory disturbances.In 2 siblings with diabetes mellitus manifestation at age under 25 years, low fasting glucose levels, severely elevated glucose levels upon glucose challenge and absent autoantibodies for IA2 and GAD clarification for MODY was sought. Mutational screening for MODY 1–3 mutations was carried out by direct sequencing followed by multiplex ligation-dependent probe amplification (MLPA).We identified a mutation within the hepatic nuclear factor 4A (HNF-4A) gene hitherto unreported for MODY-1. A causative role of the mutation is not proven, however in the 2 index patients similar phenotypes are present. These cases underline the necessity to screen for MODY when the medical history and lack of autoantibodies suggest alternative diagnoses beside type 1 diabetes.

scholarly journals Crosstalk between Macrophages and Pancreatic β-Cells in Islet Development, Homeostasis and Disease

2021 ◽  
Vol 22 (4) ◽  
pp. 1765
Author(s):  
Cristina Cosentino ◽  
Romano Regazzi
Keyword(s):  
Current Knowledge ◽  
Low Grade ◽  
Β Cells ◽  
Β Cell ◽  
Physiological Conditions ◽  
Close Proximity ◽  
Inflammatory Profile

Macrophages are highly heterogeneous and plastic immune cells with peculiar characteristics dependent on their origin and microenvironment. Following pathogen infection or damage, circulating monocytes can be recruited in different tissues where they differentiate into macrophages. Stimuli present in the surrounding milieu induce the polarisation of macrophages towards a pro-inflammatory or anti-inflammatory profile, mediating inflammatory or homeostatic responses, respectively. However, macrophages can also derive from embryonic hematopoietic precursors and reside in specific tissues, actively participating in the development and the homeostasis in physiological conditions. Pancreatic islet resident macrophages are present from the prenatal stages onwards and show specific surface markers and functions. They localise in close proximity to β-cells, being exquisite sensors of their secretory ability and viability. Over the years, the crucial role of macrophages in β-cell differentiation and homeostasis has been highlighted. In addition, macrophages are emerging as central players in the initiation of autoimmune insulitis in type 1 diabetes and in the low-grade chronic inflammation characteristic of obesity and type 2 diabetes pathogenesis. The present work reviews the current knowledge in the field, with a particular focus on the mechanisms of communication between β-cells and macrophages that have been described so far.

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