Eosinophil function in adipose tissue is regulated by Krüppel-like factor 3 (KLF3)

Knights, Alexander J.; Vohralik, Emily J.; Houweling, Peter J.; Stout, Elizabeth S.; Norton, Laura J.; Alexopoulos, Stephanie J.; Yik, Jinfen J.; Jusoh, Hanapi Mat; Olzomer, Ellen M.; Bell-Anderson, Kim; North, Klaus; Hoehn, Kyle L.; Crossley, Merlin; Quinlan, Kate

doi:10.1038/s41467-020-16758-9

Cited by 38 publications

(35 citation statements)

References 69 publications

(92 reference statements)

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“…However, macrophages within the adipose-resident compartment actually decline with age, and the proportion of pro-inflammatory macrophages increases (2,15), suggesting that despite cytokine mRNA expression, old ILC2 function is impaired and this could further compound their numerical loss. Notably, this premise of functionality versus numbers was recently demonstrated in adipose tissue eosinophils (40). We also noted enhanced expression of Ifngr1, Ifnar1, and Ifnar2 in aged ILC2 (Fig.…”

supporting

confidence: 82%

Dysregulation of adipose ILC2 underlies thermogenic failure in aging

Goldberg¹,

Shchukina²,

Youm

et al. 2020

Preprint

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Aging impairs the integrated immunometabolic responses which have evolved to maintain core body temperature in homeotherms to survive cold-stress, infections, and dietary restriction. Adipose tissue inflammation regulates the thermogenic stress response but how adipose tissue-resident cells instigate thermogenic failure in aged are unknown. Here, we define alterations in the adipose-resident immune system and identify that type 2 innate lymphoid cells (ILC2) are lost in aging. Restoration of ILC2 numbers in aged mice to levels seen in adults through IL-33 supplementation failed to rescue old mice from metabolic impairment and cold-induced lethality. Transcriptomic analyses revealed intrinsic defects in aged ILC2, and adoptive transfer of adult ILC2 are sufficient to protect old mice against cold. Thus, the functional defects in adipose ILC2 during aging drive thermogenic failure.One Sentence SummaryAge-related changes in adipose tissue drive reprogramming of ILC2 that leads to impaired cold tolerance

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supporting

confidence: 82%

Dysregulation of adipose ILC2 underlies thermogenic failure in aging

Goldberg¹,

Shchukina²,

Youm

et al. 2020

Preprint

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“…In addition to ILC2-derived IL-33-dependent eosinophils recruitment to AT, IL-33 was also shown to recruit eosinophils in the absence of ILC2s ( 178 ). It was recently demonstrated that the transcriptional repressor krüppel-like factor 3 (KLF3)-deficient mice exhibited profound WAT beiging, which was accompanied by an accumulation of AT eosinophils ( 511 ).…”

Section: The Adipose Immune System As O Regulator Of Adaptive Thermogmentioning

confidence: 99%

Adipose Tissue Immunomodulation: A Novel Therapeutic Approach in Cardiovascular and Metabolic Diseases

AlZaim

Hammoud

Al-Koussa

et al. 2020

Front. Cardiovasc. Med.

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Adipose tissue is a critical regulator of systemic metabolism and bodily homeostasis as it secretes a myriad of adipokines, including inflammatory and anti-inflammatory cytokines. As the main storage pool of lipids, subcutaneous and visceral adipose tissues undergo marked hypertrophy and hyperplasia in response to nutritional excess leading to hypoxia, adipokine dysregulation, and subsequent low-grade inflammation that is characterized by increased infiltration and activation of innate and adaptive immune cells. The specific localization, physiology, susceptibility to inflammation and the heterogeneity of the inflammatory cell population of each adipose depot are unique and thus dictate the possible complications of adipose tissue chronic inflammation. Several lines of evidence link visceral and particularly perivascular, pericardial, and perirenal adipose tissue inflammation to the development of metabolic syndrome, insulin resistance, type 2 diabetes and cardiovascular diseases. In addition to the implication of the immune system in the regulation of adipose tissue function, adipose tissue immune components are pivotal in detrimental or otherwise favorable adipose tissue remodeling and thermogenesis. Adipose tissue resident and infiltrating immune cells undergo metabolic and morphological adaptation based on the systemic energy status and thus a better comprehension of the metabolic regulation of immune cells in adipose tissues is pivotal to address complications of chronic adipose tissue inflammation. In this review, we discuss the role of adipose innate and adaptive immune cells across various physiological and pathophysiological states that pertain to the development or progression of cardiovascular diseases associated with metabolic disorders. Understanding such mechanisms allows for the exploitation of the adipose tissue-immune system crosstalk, exploring how the adipose immune system might be targeted as a strategy to treat cardiovascular derangements associated with metabolic dysfunctions.

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“…47 Additionally, eosinophils can activate beige fat cells by secreting certain factors such as KLF3, thereby reducing obesity-related disease. 48 Neutrophils are often the first immune cells to reach the site of inflamed tissue. The production of leukotriene B 4 (LTB 4) in AT promotes the accumulation of neutrophils which express IL-1β through the NF-κB pathway to cause chronic inflammation.…”

Section: Immune Cells In Obese Adipose Tissue Inflammationmentioning

confidence: 99%

<p>Characterization and Treatment of Inflammation and Insulin Resistance in Obese Adipose Tissue</p>

Song

2020

DMSO

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Adipose tissue is the largest energy storage and protection organ. It is distributed subcutaneously and around the internal organs. It regulates metabolism by storing and releasing fatty acids and secreting adipokines. Excessive nutritional intake results in adipocyte hypertrophy and proliferation, leading to local hypoxia in adipose tissue and changes in the release of adipokines. These lead to recruit of more immune cells into adipose tissue and release of inflammatory signaling factors. Excess free fatty acids and inflammatory factors interfere with intracellular insulin signaling. In this review, we summarize the characteristics of obese adipose tissue and analyze how its inflammation causes insulin resistance. We further discuss the latest clinical research progress on the control of insulin resistance and inflammation resulting from obesity through anti-inflammatory therapy and bariatric surgery. Our review shows that targeted anti-inflammatory therapy is of great significance for obese patients with insulin resistance.

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Eosinophil function in adipose tissue is regulated by Krüppel-like factor 3 (KLF3)

Cited by 38 publications

References 69 publications

Dysregulation of adipose ILC2 underlies thermogenic failure in aging

Dysregulation of adipose ILC2 underlies thermogenic failure in aging

Adipose Tissue Immunomodulation: A Novel Therapeutic Approach in Cardiovascular and Metabolic Diseases

<p>Characterization and Treatment of Inflammation and Insulin Resistance in Obese Adipose Tissue</p>

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