bims-nastce 2021-09-19 papers

Adipocyte. 2021 Dec;10(1): 435-445

The roles of T cells in obese adipose tissue inflammation.

Adipose tissue inflammation in obese patients can cause a series of metabolic diseases. There are a variety of immune cells in adipose tissue, and studies have shown that T cells are associated with adipose tissue inflammation. This review aims to describe the current understanding of the relationship between T cells and adipose tissue inflammation, with a focus on regulation by T cell subtypes. Studies have shown that Th1, Th17 and CD8+ T cells, which are important T cell subsets, can promote the development of adipose tissue inflammation, whereas Treg cells protect against inflammation, suggesting that targeting the mechanism by which T cell subtypes regulate adipose tissue inflammation is a potential therapeutic strategy for treating obesity. T cells play important roles in regulating obesity-associated adipose tissue inflammation, thus providing new research directions for the treatment of obesity. More studies are needed to clarify how T cell subtypes regulate adipose tissue inflammation to identify new treatments for obesity.

Keywords: Adipose tissue inflammation; cd4+ t cells; cd8+ t cells; treg cells

DOI: https://doi.org/10.1080/21623945.2021.1965314

Hepatol Commun. 2021 Aug 25.

The Detrimental Role of Regulatory T Cells in Nonalcoholic Steatohepatitis.

Janine Dywicki, Laura Elisa Buitrago-Molina, Fatih Noyan, Ana C Davalos-Misslitz, Katharina L Hupa-Breier, Maren Lieber, Martin Hapke, Jerome Schlue, Christine S Falk, Solaiman Raha, Immo Prinz, Christian Koenecke, Michael P Manns, Heiner Wedemeyer, Matthias Hardtke-Wolenski, Elmar Jaeckel.

Nonalcoholic steatohepatitis (NASH) is induced by steatosis and metabolic inflammation. While involvement of the innate immune response has been shown, the role of the adaptive immune response in NASH remains controversial. Likewise, the role of regulatory T cells (Treg) in NASH remains unclear although initial clinical trials aim to target these regulatory responses. High-fat high-carbohydrate (HF-HC) diet feeding of NASH-resistant BALB/c mice as well as the corresponding recombination activating 1 (Rag)-deficient strain was used to induce NASH and to study the role of the adaptive immune response. HF-HC diet feeding induced strong activation of intrahepatic T cells in BALB/c mice, suggesting an antigen-driven effect. In contrast, the effects of the absence of the adaptive immune response was notable. NASH in BALB/c Rag1-/- mice was substantially worsened and accompanied by a sharp increase of M1-like macrophage numbers. Furthermore, we found an increase in intrahepatic Treg numbers in NASH, but either adoptive Treg transfer or anti-cluster of differentiation (CD)3 therapy unexpectedly increased steatosis and the alanine aminotransferase level without otherwise affecting NASH. Conclusion: Although intrahepatic T cells were activated and marginally clonally expanded in NASH, these effects were counterbalanced by increased Treg numbers. The ablation of adaptive immunity in murine NASH led to marked aggravation of NASH, suggesting that Tregs are not regulators of metabolic inflammation but rather enhance it.

DOI: https://doi.org/10.1002/hep4.1807

Front Immunol. 2021 ;12 711217

Gut-Liver Immune Traffic: Deciphering Immune-Pathogenesis to Underpin Translational Therapy.

Amber G Bozward, Vincenzo Ronca, Daniel Osei-Bordom, Ye Htun Oo.

The tight relationship between the gut and liver on embryological, anatomical and physiological levels inspired the concept of a gut-liver axis as a central element in the pathogenesis of gut-liver axis diseases. This axis refers to the reciprocal regulation between these two organs causing an integrated system of immune homeostasis or tolerance breakdown guided by the microbiota, the diet, genetic background, and environmental factors. Continuous exposure of gut microbiome, various hormones, drugs and toxins, or metabolites from the diet through the portal vein adapt the liver to maintain its tolerogenic state. This is orchestrated by the combined effort of immune cells network: behaving as a sinusoidal and biliary firewall, along with a regulatory network of immune cells including, regulatory T cells and tolerogenic dendritic cells (DC). In addition, downregulation of costimulatory molecules on hepatic sinusoids, hepatocytes and biliary epithelial cells as well as regulating the bile acids chain also play a part in hepatic immune homeostasis. Recent evidence also demonstrated the link between changes in the gut microbiome and liver resident immune cells in the progression of cirrhosis and the tight correlation among primary sclerosing cholangitis (PSC) and also checkpoint induced liver and gut injury. In this review, we will summarize the most recent evidence of the bidirectional relationship among the gut and the liver and how it contributes to liver disease, focusing mainly on PSC and checkpoint induced hepatitis and colitis. We will also focus on completed therapeutic options and on potential targets for future treatment linking with immunology and describe the future direction of this research, taking advantage of modern technologies.

Keywords: Gut microbiota; IBD; Metabolites; PBC; PSC; liver disease; plasticity; therapy

DOI: https://doi.org/10.3389/fimmu.2021.711217

Elife. 2021 09 13. pii: e72787. [Epub ahead of print]10

Western diet shifts immune cell balance.

Christina M Bergey.

The immune cells of macaques fed a Western-like diet adopt a pro-inflammatory profile.

Keywords: behavior; diet; epidemiology; evolutionary mismatch; global health; immunology; inflammation; macaca fascicularis; monocyte

DOI: https://doi.org/10.7554/eLife.72787

J Immunother Cancer. 2021 Sep;pii: e002794. [Epub ahead of print]9(9):

Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of hepatocellular carcinoma.

Patients with advanced hepatocellular carcinoma (HCC) have historically had few options and faced extremely poor prognoses if their disease progressed after standard-of-care tyrosine kinase inhibitors (TKIs). Recently, the standard of care for HCC has been transformed as a combination of the immune checkpoint inhibitor (ICI) atezolizumab plus the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab was shown to offer improved overall survival in the first-line setting. Immunotherapy has demonstrated safety and efficacy in later lines of therapy as well, and ongoing trials are investigating novel combinations of ICIs and TKIs, in addition to interventions earlier in the course of disease or in combination with liver-directed therapies. Because HCC usually develops against a background of cirrhosis, immunotherapy for liver tumors is complex and oncologists need to account for both immunological and hepatological considerations when developing a treatment plan for their patients. To provide guidance to the oncology community on important concerns for the immunotherapeutic care of HCC, the Society for Immunotherapy of Cancer (SITC) convened a multidisciplinary panel of experts to develop a clinical practice guideline (CPG). The expert panel drew on the published literature as well as their clinical experience to develop recommendations for healthcare professionals on these important aspects of immunotherapeutic treatment for HCC, including diagnosis and staging, treatment planning, immune-related adverse events (irAEs), and patient quality of life (QOL) considerations. The evidence- and consensus-based recommendations in this CPG are intended to give guidance to cancer care providers treating patients with HCC.

Keywords: antineoplastic protocols; guidelines as topic; immunotherapy; liver neoplasms

DOI: https://doi.org/10.1136/jitc-2021-002794

Proc Natl Acad Sci U S A. 2021 Sep 21. pii: e2106630118. [Epub ahead of print]118(38):

Identifying extracellular vesicle populations from single cells.

Jonas M Nikoloff, Mario A Saucedo-Espinosa, André Kling, Petra S Dittrich.

Extracellular vesicles (EVs) are constantly secreted from both eukaryotic and prokaryotic cells. EVs, including those referred to as exosomes, may have an impact on cell signaling and an incidence in diseased cells. In this manuscript, a platform to capture, quantify, and phenotypically classify the EVs secreted from single cells is introduced. Microfluidic chambers of about 300 pL are employed to trap and isolate individual cells. The EVs secreted within these chambers are then captured by surface-immobilized monoclonal antibodies (mAbs), irrespective of their intracellular origin. Immunostaining against both plasma membrane and cytosolic proteins was combined with highly sensitive, multicolor total internal reflection fluorescence microscopy to characterize the immobilized vesicles. The data analysis of high-resolution images allowed the assignment of each detected EV to one of 15 unique populations and demonstrated the presence of highly heterogeneous phenotypes even at the single-cell level. The analysis also revealed that each mAb isolates phenotypically different EVs and that more vesicles were effectively immobilized when CD63 was targeted instead of CD81. Finally, we demonstrate how a heterogeneous suppression in the secreted vesicles is obtained when the enzyme neutral sphingomyelinase is inhibited.

Keywords: extracellular vesicles; microfluidics; single-cell analysis

DOI: https://doi.org/10.1073/pnas.2106630118