scholarly journals Stromal cells maintain immune cell homeostasis in adipose tissue via production of interleukin-33

2019 ◽  
Vol 4 (35) ◽  
pp. eaax0416 ◽  
Author(s):  
T. Mahlakõiv ◽  
A.-L. Flamar ◽  
L. K. Johnston ◽  
S. Moriyama ◽  
G. G. Putzel ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Progenitor Cells ◽  
Stromal Cells ◽  
Immune Cell ◽  
Cell Activity ◽  
Lymphoid Cells ◽  
Immune Homeostasis ◽  
Low Grade ◽  
Interleukin 33 ◽  
Group 2

Obesity is driven by chronic low-grade inflammation resulting from dysregulated immune cell accumulation and function in white adipose tissue (WAT). Interleukin-33 (IL-33) is a key cytokine that controls innate and adaptive immune cell activity and immune homeostasis in WAT, although the sources of IL-33 have remained controversial. Here, we show that WAT-resident mesenchyme-derived stromal cells are the dominant producers of IL-33. Adipose stem and progenitor cells (ASPCs) produced IL-33 in all WAT depots, whereas mesothelial cells served as an additional source of IL-33 in visceral WAT. ASPC-derived IL-33 promoted a regulatory circuit that maintained an immune tone in WAT via the induction of group 2 innate lymphoid cell–derived type 2 cytokines and maintenance of eosinophils, whereas mesothelial IL-33 also acted as an alarmin by inducing peritoneal immune response upon infection. Together, these data reveal a previously unrecognized regulatory network between tissue-resident progenitor cells and innate lymphoid cells that maintains immune homeostasis in adipose tissue.

scholarly journals DR3 stimulation of adipose resident ILC2s ameliorates type 2 diabetes mellitus

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Pedram Shafiei-Jahani ◽  
Benjamin P. Hurrell ◽  
Lauriane Galle-Treger ◽  
Doumet Georges Helou ◽  
Emily Howard ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Adipose Tissue ◽  
Death Receptor ◽  
Lymphoid Cells ◽  
Low Grade ◽  
Group 2

Abstract Disturbances in glucose homeostasis and low-grade chronic inflammation culminate into metabolic syndrome that increase the risk for the development of type 2 diabetes mellitus (T2DM). The recently discovered group 2 innate lymphoid cells (ILC2s) are capable of secreting copious amounts of type 2 cytokines to modulate metabolic homeostasis in adipose tissue. In this study, we have established that expression of Death Receptor 3 (DR3), a member of the TNF superfamily, on visceral adipose tissue (VAT)-derived murine and peripheral blood human ILC2s is inducible by IL-33. We demonstrate that DR3 engages the canonical and/or non-canonical NF-κB pathways, and thus stimulates naïve and co-stimulates IL-33-activated ILC2s. Importantly, DR3 engagement on ILC2s significantly ameliorates glucose tolerance, protects against insulin-resistance onset and remarkably reverses already established insulin-resistance. Taken together, these results convey the potent role of DR3 as an ILC2 regulator and introduce DR3 agonistic treatment as a novel therapeutic avenue for treating T2DM.

scholarly journals A stromal cell niche sustains ILC2-mediated type-2 conditioning in adipose tissue

2019 ◽  
Vol 216 (9) ◽  
pp. 1999-2009 ◽  
Author(s):  
Batika M.J. Rana ◽  
Eric Jou ◽  
Jillian L. Barlow ◽  
Noe Rodriguez-Rodriguez ◽  
Jennifer A. Walker ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Immune Cells ◽  
Stromal Cells ◽  
Stromal Cell ◽  
Cell Stress ◽  
Lymphoid Cells ◽  
Type 2 Cytokines ◽  
Group 2 ◽  
Cell Niche

Group-2 innate lymphoid cells (ILC2), type-2 cytokines, and eosinophils have all been implicated in sustaining adipose tissue homeostasis. However, the interplay between the stroma and adipose-resident immune cells is less well understood. We identify that white adipose tissue–resident multipotent stromal cells (WAT-MSCs) can act as a reservoir for IL-33, especially after cell stress, but also provide additional signals for sustaining ILC2. Indeed, we demonstrate that WAT-MSCs also support ICAM-1–mediated proliferation and activation of LFA-1–expressing ILC2s. Consequently, ILC2-derived IL-4 and IL-13 feed back to induce eotaxin secretion from WAT-MSCs, supporting eosinophil recruitment. Thus, MSCs provide a niche for multifaceted dialogue with ILC2 to sustain a type-2 immune environment in WAT.

Fertile Potential of Freshly Isolated Adipose Tissue Derived Stromal cells and Bone Marrow Mesenchymal Stromal cells Against Premature Ovarian Failure

2021 ◽  
Vol 17 ◽  
Author(s):  
Tahir Maqbool ◽  
Faheem Hadi ◽  
Sehrish Tahir ◽  
Sadia Naz ◽  
Sajida Shahnawaz ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Adipose Tissue ◽  
Mesenchymal Stromal Cells ◽  
Premature Ovarian Failure ◽  
Stromal Cells ◽  
Serum Levels ◽  
Ovarian Failure ◽  
Group 4 ◽  
Group 3 ◽  
Group 2

Background: Failure to attain pregnancy or even miscarriage leads to infertility and premature ovarian failure (POF) is challenging type of infertility, stem cells have the ability to repair ovarian damage adipose tissue derived stromal cells (AT-SCs) and bone marrow mesenchymal stromal cells (BM-MSCs) have demonstrated promising regenerative abilities in several diseases including POF. Methods: Experiments were performed to prove the ability of AT-SCs and BM-MSCs in restoring ovarian functions, a total of 20 rats were randomly assigned to four groups; 5 rats in each group 1st group was untreated, 2nd was cyclophosphamide and busulfan treated group, 3rd was cyclophosphamide and busulfan + AT-SCs, 4th was cyclophosphamide and busulfan + BM-MSCs. Results: Group 3 and group 4 showed restored ovarian functions in the form of increase of weight (including body weight and ovarian weight), and a significant decrease in FSH serum levels (p < 0.05) compared to group 2, and anti-Mullerian hormone (AMH) serum levels increased (p < 0.05) in group 3 and group 4 versus group 2. Increased antioxidant level of glutathione (GSH) and superoxide dismutase (SOD) in group 3 and group 4 compared with group 2, also histochemistry analysis demonstrated normal tissue distribution in 3rd and 4th group compared with 2nd group. Conclusions: We demonstrated the ability of AT-SCs and BM-MSCs to restore ovarian function in female with POF.

scholarly journals NLRP3 Inflammasome Activation in Adipose Tissues and Its Implications on Metabolic Diseases

2020 ◽  
Vol 21 (11) ◽  
pp. 4184 ◽  
Author(s):  
Kelvin Ka-Lok Wu ◽  
Samson Wing-Ming Cheung ◽  
Kenneth King-Yip Cheng
Keyword(s):  
Adipose Tissue ◽  
Nlrp3 Inflammasome ◽  
Metabolic Disorders ◽  
Immune Cell ◽  
Diabetic Patients ◽  
Inflammasome Activation ◽  
Low Grade ◽  
Adipose Tissues ◽  
Adipose Tissue Dysfunction ◽  
Nlrp3 Inflammasome Activation

Adipose tissue is an active endocrine and immune organ that controls systemic immunometabolism via multiple pathways. Diverse immune cell populations reside in adipose tissue, and their composition and immune responses vary with nutritional and environmental conditions. Adipose tissue dysfunction, characterized by sterile low-grade chronic inflammation and excessive immune cell infiltration, is a hallmark of obesity, as well as an important link to cardiometabolic diseases. Amongst the pro-inflammatory factors secreted by the dysfunctional adipose tissue, interleukin (IL)-1β, induced by the NLR family pyrin domain-containing 3 (NLRP3) inflammasome, not only impairs peripheral insulin sensitivity, but it also interferes with the endocrine and immune functions of adipose tissue in a paracrine manner. Human studies indicated that NLRP3 activity in adipose tissues positively correlates with obesity and its metabolic complications, and treatment with the IL-1β antibody improves glycaemia control in type 2 diabetic patients. In mouse models, genetic or pharmacological inhibition of NLRP3 activation pathways or IL-1β prevents adipose tissue dysfunction, including inflammation, fibrosis, defective lipid handling and adipogenesis, which in turn alleviates obesity and its related metabolic disorders. In this review, we summarize both the negative and positive regulators of NLRP3 inflammasome activation, and its pathophysiological consequences on immunometabolism. We also discuss the potential therapeutic approaches to targeting adipose tissue inflammasome for the treatment of obesity and its related metabolic disorders.

scholarly journals Aerobic training reduces immune cell recruitment and cytokine levels in adipose tissue in obese mice

2019 ◽  
Vol 44 (5) ◽  
pp. 512-520 ◽  
Author(s):  
Débora Romualdo Lacerda ◽  
Michele Macedo Moraes ◽  
Albená Nunes-Silva ◽  
Kátia Anunciação Costa ◽  
Débora Fernandes Rodrigues ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Immune Cells ◽  
Aerobic Training ◽  
Immune Cell ◽  
Control Diet ◽  
Moderate Intensity ◽  
Low Grade ◽  
Carbohydrate Diet ◽  
Cytokine Levels ◽  
Low Grade Inflammation

Obesity is associated with an energy imbalance that results from excessive energy intake, low diet quality, and a sedentary lifestyle. The increased consumption of a high-refined carbohydrate (HC) diet is strongly related to higher adiposity and low-grade inflammation. Aerobic training is a well-known nonpharmacological intervention to treat obesity and metabolic disturbances. However, the mechanisms through which aerobic training ameliorates the low-grade inflammation induced by an HC diet should be further investigated. Our hypothesis herein was that aerobic training would decrease the recruitment of leukocytes in adipose tissue, thereby reducing the levels of cytokines and improving metabolism in mice fed an HC diet. Male Balb/c mice were assigned to the following groups: control diet/nontrained (C-NT), control diet/trained (C-T), high-refined carbohydrate diet/nontrained (HC-NT), and high-refined carbohydrate diet/trained (HC-T). Mice were submitted to moderate-intensity training sessions that consisted of running 60 min per day for 8 weeks. An intravital microscopy technique was performed in vivo in anesthetized mice to visualize the microvasculature of the adipose tissue. The HC diet induced obesity and increased the influx of immune cells into the adipose tissue. In contrast, HC-T mice presented a lower adiposity and adipocyte area. Furthermore, relative to HC-NT mice, HC-T mice showed increased resting energy expenditure, decreased recruitment of immune cells in the adipose tissue, reduced cytokine levels, and ameliorated hyperglycemia and fatty liver deposition. Collectively, our data enhance understanding about the anti-inflammatory effect of aerobic training and shed light on the adipose tissue-mediated mechanisms by which training promotes a healthier metabolic profile.

scholarly journals The essential function of IL-33 in metabolic regulation

2020 ◽  
Vol 52 (7) ◽  
pp. 768-775 ◽  
Author(s):  
Wenping Li ◽  
Yiyuan Li ◽  
Jin Jin
Keyword(s):  
Metabolic Regulation ◽  
Underlying Mechanism ◽  
Lymphoid Cells ◽  
Regulatory Function ◽  
Current Evidence ◽  
Metabolic Processes ◽  
Interleukin 33 ◽  
Health And Disease ◽  
Essential Function ◽  
Group 2

Abstract Interleukin-33 (IL-33) is produced by various types of cells under physical or pathological conditions. As a multifunctional partner in health and disease, current evidence reveals that IL-33 also participates in several metabolic processes. IL-33 has been proven to contribute to regulating the activity of ST2+ group 2 innate lymphoid cells and regulatory T cells in adipose, which leads to the shift of insulin sensitivity and glucose clearance in glucose metabolism, thermogenesis, and adipocyte beiging in adipose metabolism. In this review, we briefly summarize the biological characteristics of Il-33 and discuss its regulatory function in glucose and adipose metabolism. By clarifying the underlying mechanism of IL-33, we highlight the crosstalk between immune response and metabolic processes mediated by IL-33.

scholarly journals IN VITRO ACTIVATION OF CELLULAR IMMUNE RESPONSE TO GROSS VIRUS-INDUCED LYMPHOMA

1972 ◽  
Vol 136 (5) ◽  
pp. 969-983 ◽  
Author(s):  
Manuel Ortiz de Landazuri ◽  
Ronald B. Herberman
Keyword(s):  
Immune Cells ◽  
Immune Cell ◽  
Cell Activity ◽  
Surface Characteristics ◽  
Immune Serum ◽  
Lymphoid Cells ◽  
Rat Serum ◽  
In Vitro Incubation ◽  
Central Inhibition

Spleen cells from W/Fu rats 40 days or more after immunization with a syngeneic Gross virus-induced leukemia were unreactive in direct cytotoxic assays. Incubation of these immune cells at 37°C for 12 hr or longer, in the absence of antigen, resulted in the appearance of specific cytotoxic reactivity. Other lymphoid cells from the immune rats also were activated upon in vitro incubation, but to a lesser extent. Experiments were performed to define the necessary conditions and the mechanism for the in vitro incubation. Activation was temperature dependent, occurring at 37°C but not at 4°C. Immune serum suppressed the activation, but normal rat serum also had some inhibitory activity. Passage of immune cells through a nylon column, before preincubation, prevented activation. In contrast, exposure to nylon after preincubation did not remove cytotoxic reactivity. These findings demonstrate the reversal of a central inhibition of immune cell activity. The explanations offered for this phenomenon included change in surface characteristics of the immune cells during in vitro incubation, and the possible need for an adherent helper cell.

scholarly journals Acetylcholine production by group 2 innate lymphoid cells promotes mucosal immunity to helminths

2021 ◽  
Vol 6 (57) ◽  
pp. eabd0359
Author(s):  
Luke B. Roberts ◽  
Corinna Schnoeller ◽  
Rita Berkachy ◽  
Matthew Darby ◽  
Jamie Pillaye ◽  
...  
Keyword(s):  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Mucosal Barrier ◽  
Nippostrongylus Brasiliensis ◽  
Interleukin 33 ◽  
Group 2 ◽  
Maximal Induction

Innate lymphoid cells (ILCs) are critical mediators of immunological and physiological responses at mucosal barrier sites. Whereas neurotransmitters can stimulate ILCs, the synthesis of small-molecule neurotransmitters by these cells has only recently been appreciated. Group 2 ILCs (ILC2s) are shown here to synthesize and release acetylcholine (ACh) during parasitic nematode infection. The cholinergic phenotype of pulmonary ILC2s was associated with their activation state, could be induced by in vivo exposure to extracts of Alternaria alternata or the alarmin cytokines interleukin-33 (IL-33) and IL-25, and was augmented by IL-2 in vitro. Genetic disruption of ACh synthesis by murine ILC2s resulted in increased parasite burdens, lower numbers of ILC2s, and reduced lung and gut barrier responses to Nippostrongylus brasiliensis infection. These data demonstrate a functional role for ILC2-derived ACh in the expansion of ILC2s for maximal induction of type 2 immunity.

scholarly journals Leukocyte Heterogeneity in Adipose Tissue, Including in Obesity

2020 ◽  
Vol 126 (11) ◽  
pp. 1590-1612 ◽  
Author(s):  
Ada Weinstock ◽  
Hernandez Moura Silva ◽  
Kathryn J. Moore ◽  
Ann Marie Schmidt ◽  
Edward A. Fisher
Keyword(s):  
Adipose Tissue ◽  
Immune Cells ◽  
Immune Cell ◽  
Γδ T Cells ◽  
The United States ◽  
Low Grade ◽  
Obesity Prevalence ◽  
Cell Level ◽  
Mortality And Morbidity ◽  
Molecular Investigation

Adipose tissue (AT) plays a central role in both metabolic health and pathophysiology. Its expansion in obesity results in increased mortality and morbidity, with contributions to cardiovascular disease, diabetes mellitus, fatty liver disease, and cancer. Obesity prevalence is at an all-time high and is projected to be 50% in the United States by 2030. AT is home to a large variety of immune cells, which are critical to maintain normal tissue functions. For example, γδ T cells are fundamental for AT innervation and thermogenesis, and macrophages are required for recycling of lipids released by adipocytes. The expansion of visceral white AT promotes dysregulation of its immune cell composition and likely promotes low-grade chronic inflammation, which has been proposed to be the underlying cause for the complications of obesity. Interestingly, weight loss after obesity alters the AT immune compartment, which may account for the decreased risk of developing these complications. Recent technological advancements that allow molecular investigation on a single-cell level have led to the discovery of previously unappreciated heterogeneity in many organs and tissues. In this review, we will explore the heterogeneity of immune cells within the visceral white AT and their contributions to homeostasis and pathology.

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