The rising number of obese individuals has become a major burden to the healthcare systems worldwide. Obesity includes not only the increase of adipose tissue mass but importantly also the altered cellular functions that collectively lead to a chronic state of adipose tissue inflammation, insulin resistance and impaired wound healing. Adipose tissue undergoing chronic inflammation shows altered cytokine expression and an accumulation of adipose tissue macrophages (ATM). The macrophage migration inhibitory factor (MIF) superfamily consists of MIF and the recently identified homolog D-dopachrome tautomerase (D-DT or MIF-2). MIF and D-DT, which both bind to the CD74/CD44 receptor complex, are differentially expressed in adipose tissue and have distinct roles in adipogenesis. MIF positively correlates with obesity as well as insulin resistance and contributes to adipose tissue inflammation by modulating ATM functions. D-DT, however, is negatively correlated with obesity and reverses glucose intolerance. In this review, their respective roles in adipose tissue homeostasis, adipose tissue inflammation, insulin resistance and impaired wound healing will be reviewed.
Adipose Tissue/*immunology/pathology ; Animals ; Diabetes Mellitus/immunology/pathology ; Humans ; Inflammation/*immunology/pathology ; Insulin Resistance ; Intramolecular Oxidoreductases/analysis/*immunology ; Macrophage Migration-Inhibitory Factors/analysis/*immunology ; Macrophages/immunology/pathology ; Obesity/*immunology/pathology ; *Wound Healing

The rising number of obese individuals has become a major burden to the healthcare systems worldwide. Obesity includes not only the increase of adipose tissue mass but importantly also the altered cellular functions that collectively lead to a chronic state of adipose tissue inflammation, insulin resistance and impaired wound healing. Adipose tissue undergoing chronic inflammation shows altered cytokine expression and an accumulation of adipose tissue macrophages (ATM). The macrophage migration inhibitory factor (MIF) superfamily consists of MIF and the recently identified homolog D-dopachrome tautomerase (D-DT or MIF-2). MIF and D-DT, which both bind to the CD74/CD44 receptor complex, are differentially expressed in adipose tissue and have distinct roles in adipogenesis. MIF positively correlates with obesity as well as insulin resistance and contributes to adipose tissue inflammation by modulating ATM functions. D-DT, however, is negatively correlated with obesity and reverses glucose intolerance. In this review, their respective roles in adipose tissue homeostasis, adipose tissue inflammation, insulin resistance and impaired wound healing will be reviewed.
Adipose Tissue/*immunology/pathology ; Animals ; Diabetes Mellitus/immunology/pathology ; Humans ; Inflammation/*immunology/pathology ; Insulin Resistance ; Intramolecular Oxidoreductases/analysis/*immunology ; Macrophage Migration-Inhibitory Factors/analysis/*immunology ; Macrophages/immunology/pathology ; Obesity/*immunology/pathology ; *Wound Healing

White fat cells secrete adipokines that induce inflammation and obesity has been reported to be characterized by high serum levels of inflammatory cytokines such as IL-6 and TNF-alpha. Rheumatoid arthritis (RA) is a prototype of inflammatory arthritis, but the relationship between RA and obesity is controversial. We made an obese inflammatory arthritis model: obese collagen-induced arthritis (CIA). C57BL/6 mice were fed a 60-kcal high fat diet (HFD) from the age of 4 weeks and they were immunized twice with type II collagen (CII). After immunization, the obese CIA mice showed higher arthritis index scores and histology scores and a more increased incidence of developing arthritis than did the lean CIA mice. After treatment with CII, mixed lymphocyte reaction also showed CII-specific response more intensely in the obese CIA mice than lean CIA. The anti-CII IgG and anti-CII IgG2a levels in the sera of the obese CIA mice were higher than those of the lean CIA mice. The number of Th17 cells was higher and the IL-17 mRNA expression of the splenocytes in the obese CIA mice was higher than that of the lean CIA mice. Obese CIA mice also showed high IL-17 expression on synovium in immunohistochemistry. Although obesity may not play a pathogenic role in initiating arthritis, it could play an important role in amplifying the inflammation of arthritis through the Th1/Th17 response. The obese CIA murine model will be an important tool when we investigate the effect of several therapeutic target molecules to treat RA.
Adipokines/immunology/metabolism ; Animals ; *Arthritis, Experimental/genetics/immunology/pathology ; Cell Differentiation/genetics/immunology ; *Collagen Type II/administration & dosage/immunology ; Disease Models, Animal ; Gene Expression ; Humans ; Inflammation/chemically induced/*immunology ; Interleukin-17/metabolism ; Interleukin-6/blood ; Joints/immunology/pathology ; Mice ; Mice, Inbred C57BL ; *Obesity/genetics/immunology/pathology ; *Th17 Cells/immunology/metabolism ; Tumor Necrosis Factor-alpha/blood

Due to their high immunostimulatory ability as well as the critical role they play in the maintenance of self-tolerance, dendritic cells have been implicated in the pathogenesis of autoimmune diseases. The non-obese diabetic (NOD) mouse is an animal model of autoimmune type 1 diabetes, in which pancreatic beta cells are selectively destroyed mainly by T cell-mediated immune responses. To elucidate initiation mechanisms of beta cell-specific autoimmunity, we attempted to generate bone marrow-derived dendritic cells from NOD mice. However, our results showed low proliferative response of NOD bone marrow cells and some defects in the differentiation into the myeloid dendritic cells. NOD dendritic cells showed lower expressions of MHC class II, B7-1, B7-2 and CD40, compared with C57BL/6 dendritic cells. In mixed lymphocyte reactions, stimulatory activities of NOD dendritic cells were also weak. Treatment with LPS, INF-gamma and anti-CD40 stimulated NOD dendritic cells to produce IL-12p70. The amount of IL-12, however, appeared to be lower than that of C57BL/6. Results of the present study indicated that there may be some defects in the development of NOD dendritic cells in the bone marrow, which might have an impact on the breakdown of self tolerance.
Animal ; Autoimmune Diseases/pathology ; Autoimmune Diseases/immunology ; Bone Marrow Cells/pathology* ; Bone Marrow Cells/immunology* ; Bone Marrow Cells/chemistry ; Cell Differentiation/immunology ; Cell Differentiation/drug effects ; Dendritic Cells/pathology* ; Dendritic Cells/immunology* ; Dendritic Cells/chemistry ; Diabetes Mellitus, Insulin-Dependent/pathology* ; Diabetes Mellitus, Insulin-Dependent/immunology ; Enzyme-Linked Immunosorbent Assay ; Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology ; Interleukin-12/analysis ; Interleukin-4/pharmacology ; Lipopolysaccharides/pharmacology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Inbred NOD ; Obesity

INTRODUCTION: Pregnant women are reported to be at increased risk of severe coronavirus disease 2019 (COVID-19) due to underlying immunosuppression during pregnancy. However, the clinical course of COVID-19 in pregnancy and risk of vertical and horizontal transmission remain relatively unknown. We aim to describe and evaluate outcomes in pregnant women with COVID-19 in Singapore. METHODS: Prospective observational study of 16 pregnant patients admitted for COVID-19 to 4 tertiary hospitals in Singapore. Outcomes included severe disease, pregnancy loss, and vertical and horizontal transmission. RESULTS: Of the 16 patients, 37.5%, 43.8% and 18.7% were infected in the first, second and third trimesters, respectively. Two gravidas aged ≥35 years (12.5%) developed severe pneumonia; one patient (body mass index 32.9kg/m2) required transfer to intensive care. The median duration of acute infection was 19 days; one patient remained reverse transcription polymerase chain reaction (RT-PCR) positive >11 weeks from diagnosis. There were no maternal mortalities. Five pregnancies produced term live-births while 2 spontaneous miscarriages occurred at 11 and 23 weeks. RT-PCR of breast milk and maternal and neonatal samples taken at birth were negative; placenta and cord histology showed non-specific inflammation; and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immunoglobulins were elevated in paired maternal and umbilical cord blood (n=5). CONCLUSION The majority of COVID-19 infected pregnant women had mild disease and only 2 women with risk factors (obesity, older age) had severe infection; this represents a slightly higher incidence than observed in age-matched non-pregnant women. Among the women who delivered, there was no definitive evidence of mother-to-child transmission via breast milk or placenta.
Abortion, Spontaneous/epidemiology* ; Adult ; COVID-19/transmission* ; COVID-19 Nucleic Acid Testing ; COVID-19 Serological Testing ; Cohort Studies ; Disease Transmission, Infectious/statistics & numerical data* ; Female ; Fetal Blood/immunology* ; Humans ; Infectious Disease Transmission, Vertical/statistics & numerical data* ; Live Birth/epidemiology* ; Maternal Age ; Milk, Human/virology* ; Obesity, Maternal/epidemiology* ; Placenta/pathology* ; Pregnancy ; Pregnancy Complications, Infectious/physiopathology* ; Pregnancy Outcome/epidemiology* ; Pregnancy Trimester, First ; Pregnancy Trimester, Second ; Prospective Studies ; RNA, Viral/analysis* ; Risk Factors ; SARS-CoV-2 ; Severity of Illness Index ; Singapore/epidemiology* ; Umbilical Cord/pathology* ; Young Adult