bims-adipim Biomed News
on Adipose immunity and immunometabolism
Issue of 2023–07–16
six papers selected by
Matthew C. Sinton, University of Glasgow
  1. Defining subpopulations of human adipose tissue progenitor cells.
  2. High-fat-diet-associated intestinal microbiota exacerbates psoriasis-like inflammation by enhancing systemic γδ T cell IL-17 production.
  3. Transcription factor EGR2 controls homing and pathogenicity of TH17 cells in the central nervous system.
  4. Combined cerebrospinal fluid metabolomic and cytokine profiling in tuberculosis meningitis reveals robust and prolonged changes in immunometabolic networks.
  5. Physiological role of cytokines in the regulation of mammalian metabolism.
  6. Adipokines regulate mesenchymal stem cell osteogenic differentiation.
  1. Nat Rev Endocrinol. 2023 Jul 10.
    Defining subpopulations of human adipose tissue progenitor cells.
    Claire Greenhill.
      
    DOI:  https://doi.org/10.1038/s41574-023-00876-7
  2. Cell Rep. 2023 Jul 06. pii: S2211-1247(23)00724-6. [Epub ahead of print]42(7): 112713
    High-fat-diet-associated intestinal microbiota exacerbates psoriasis-like inflammation by enhancing systemic γδ T cell IL-17 production.
    Koshiro Sonomoto, Rui Song, Daniel Eriksson, Anne M Hahn, Xianyi Meng, Pang Lyu, Shan Cao, Ning Liu, R Verena Taudte, Stefan Wirtz, Yoshiya Tanaka, Thomas H Winkler, Georg Schett, Didier Soulat, Aline Bozec.
      Although it is known that psoriasis is strongly associated with obesity, the mechanistic connection between diet and skin lesions is not well established. Herein, we showed that only dietary fat, not carbohydrates or proteins, exacerbates psoriatic disease. Enhanced psoriatic skin inflammation was associated with changes in the intestinal mucus layer and microbiota composition by high-fat diet (HFD). Change of intestinal microbiota by vancomycin treatment effectively blocked activation of psoriatic skin inflammation by HFD, inhibited the systemic interleukin-17 (IL-17) response, and led to increased mucophilic bacterial species such as Akkermansia muciniphila. By using IL-17 reporter mice, we could show that HFD facilitates IL-17-mediated γδ T cell response in the spleen. Notably, oral gavage with live or heat-killed A. muciniphila effectively inhibited HFD-induced enhancement of psoriatic disease. In conclusion, HFD exacerbates psoriatic skin inflammation through changing the mucus barrier and the intestine microbial composition, which leads to an enhanced systemic IL-17 response.
    Keywords:  CP: Immunology; CP: Microbiology; high-fat diet; psoriasis; γδT cell
    DOI:  https://doi.org/10.1016/j.celrep.2023.112713
  3. Nat Immunol. 2023 Jul 13.
    Transcription factor EGR2 controls homing and pathogenicity of TH17 cells in the central nervous system.
    Yuanyuan Gao, Yan Wang, Daniel Chauss, Alejandro V Villarino, Verena M Link, Hiroyuki Nagashima, Camille A Spinner, Vishal N Koparde, Nicolas Bouladoux, Michael S Abers, Timothy J Break, Laura B Chopp, Jung-Hyun Park, Jinfang Zhu, David L Wiest, Warren J Leonard, Michail S Lionakis, John J O'Shea, Behdad Afzali, Yasmine Belkaid, Vanja Lazarevic.
      CD4+ T helper 17 (TH17) cells protect barrier tissues but also trigger autoimmunity. The mechanisms behind these opposing processes remain unclear. Here, we found that the transcription factor EGR2 controlled the transcriptional program of pathogenic TH17 cells in the central nervous system (CNS) but not that of protective TH17 cells at barrier sites. EGR2 was significantly elevated in myelin-reactive CD4+ T cells from patients with multiple sclerosis and mice with autoimmune neuroinflammation. The EGR2 transcriptional program was intricately woven within the TH17 cell transcriptional regulatory network and showed high interconnectivity with core TH17 cell-specific transcription factors. Mechanistically, EGR2 enhanced TH17 cell differentiation and myeloid cell recruitment to the CNS by upregulating pathogenesis-associated genes and myelomonocytic chemokines. T cell-specific deletion of Egr2 attenuated neuroinflammation without compromising the host's ability to control infections. Our study shows that EGR2 regulates tissue-specific and disease-specific functions in pathogenic TH17 cells in the CNS.
    DOI:  https://doi.org/10.1038/s41590-023-01553-7
  4. medRxiv. 2023 Jun 29. pii: 2023.06.26.23291676. [Epub ahead of print]
    Combined cerebrospinal fluid metabolomic and cytokine profiling in tuberculosis meningitis reveals robust and prolonged changes in immunometabolic networks.
    Jeff Tomalka, Ashish Sharma, Alison G C Smith, Teona Avaliani, Mariam Gujabidze, Tinatin Bakuradze, Shorena Sabanadze, Dean P Jones, Zaza Avaliani, Maia Kipiani, Russell R Kempker, Jeffrey M Collins.
      Much of the high mortality in tuberculosis meningitis (TBM) is attributable to excessive inflammation, making it imperative to identify targets for host-directed therapies that reduce pathologic inflammation and mortality. In this study, we investigate how cytokines and metabolites in the cerebral spinal fluid (CSF) associate with TBM at diagnosis and during TBM treatment. At diagnosis, TBM patients demonstrate significant increases versus controls of cytokines and chemokines that promote inflammation and cell migration including IL-17A, IL-2, TNFα, IFNγ, and IL-1β. Inflammatory immune signaling was strongly correlated with immunomodulatory metabolites including kynurenine, lactic acid, carnitine, tryptophan, and itaconate. Inflammatory immunometabolic networks were only partially reversed with two months of effective TBM treatment and remained significantly different versus control CSF. Together, these data highlight a critical role for host metabolism in regulating the inflammatory response to TBM and indicate the timeline for restoration of immune homeostasis in the CSF is prolonged.
    DOI:  https://doi.org/10.1101/2023.06.26.23291676
  5. Trends Immunol. 2023 Jul 07. pii: S1471-4906(23)00110-2. [Epub ahead of print]
    Physiological role of cytokines in the regulation of mammalian metabolism.
    Axel de Baat, Beckey Trinh, Helga Ellingsgaard, Marc Y Donath.
      The innate cytokine system is involved in the response to excessive food intake. In this review, we highlight recent advances in our understanding of the physiological role of three prominent cytokines, interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF), in mammalian metabolic regulation. This recent research highlights the pleiotropic and context-dependent functions in the immune-metabolic interplay. IL-1β is activated in response to overloaded mitochondrial metabolism, stimulates insulin secretion, and allocates energy to immune cells. IL-6 is released by contracting skeletal muscle and adipose tissue and directs energy from storing tissues to consuming tissues. TNF induces insulin resistance and prevents ketogenesis. Additionally, the therapeutic potential of modulating the activity of each cytokine is discussed.
    Keywords:  cytokine; diabetes; humans; insulin; metabolism; obesity
    DOI:  https://doi.org/10.1016/j.it.2023.06.002
  6. World J Stem Cells. 2023 Jun 26. 15(6): 502-513
    Adipokines regulate mesenchymal stem cell osteogenic differentiation.
    Zhong-Hua Xu, Chen-Wei Xiong, Kai-Song Miao, Zhen-Tang Yu, Jun-Jie Zhang, Chang-Lin Yu, Yong Huang, Xin-Die Zhou.
      Mesenchymal stem cells (MSCs) can differentiate into various tissue cell types including bone, adipose, cartilage, and muscle. Among those, osteogenic differentiation of MSCs has been widely explored in many bone tissue engineering studies. Moreover, the conditions and methods of inducing osteogenic differentiation of MSCs are continuously advancing. Recently, with the gradual recognition of adipokines, the research on their involvement in different pathophysiological processes of the body is also deepening including lipid metabolism, inflammation, immune regulation, energy disorders, and bone homeostasis. At the same time, the role of adipokines in the osteogenic differentiation of MSCs has been gradually described more completely. Therefore, this paper reviewed the evidence of the role of adipokines in the osteogenic differentiation of MSCs, emphasizing bone formation and bone regeneration.
    Keywords:  Adipokines; Adipose tissue; Bone regeneration; Mesenchymal stem cells; Osteogenesis; Osteogenic differentiation
    DOI:  https://doi.org/10.4252/wjsc.v15.i6.502
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