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Your search keyword '"McKenzie, Andrew NJ"' showing total 3 results
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3 results on '"McKenzie, Andrew NJ"'

1. Group 2 Innate Lymphoid Cells Are Redundant in Experimental Renal Ischemia-Reperfusion Injury

Author

Cameron, Guy JM, Cautivo, Kelly M, Loering, Svenja, Jiang, Simon H, Deshpande, Aniruddh V, Foster, Paul S, McKenzie, Andrew NJ, Molofsky, Ari B, Hansbro, Philip M, and Starkey, Malcolm R

Subjects
Medical Physiology, Biomedical and Clinical Sciences, Clinical Sciences, Kidney Disease, Aetiology, 2.1 Biological and endogenous factors, Renal and urogenital, Acute Kidney Injury, Animals, Biomarkers, Disease Susceptibility, Humans, Kidney, Lymphocytes, Obesity, Reperfusion Injury, Respiratory Tract Diseases, ILC2, group 2 innate lymphoid cell, IL-5, IL-13, kidney, renal, IRI, ischemia-reperfusion injury, Immunology, Medical Microbiology, Biochemistry and cell biology, Genetics
Abstract

Acute kidney injury (AKI) can be fatal and is a well-defined risk factor for the development of chronic kidney disease. Group 2 innate lymphoid cells (ILC2s) are innate producers of type-2 cytokines and are critical regulators of homeostasis in peripheral organs. However, our knowledge of their function in the kidney is relatively limited. Recent evidence suggests that increasing ILC2 numbers by systemic administration of recombinant interleukin (IL)-25 or IL-33 protects against renal injury. Whilst ILC2s can be induced to protect against ischemic- or chemical-induced AKI, the impact of ILC2 deficiency or depletion on the severity of renal injury is unknown. Firstly, the phenotype and location of ILC2s in the kidney was assessed under homeostatic conditions. Kidney ILC2s constitutively expressed high levels of IL-5 and were located in close proximity to the renal vasculature. To test the functional role of ILC2s in the kidney, an experimental model of renal ischemia-reperfusion injury (IRI) was used and the severity of injury was assessed in wild-type, ILC2-reduced, ILC2-deficient, and ILC2-depleted mice. Surprisingly, there were no differences in histopathology, collagen deposition or mRNA expression of injury-associated (Lcn2), inflammatory (Cxcl1, Cxcl2, and Tnf) or extracellular matrix (Col1a1, Fn1) factors following IRI in the absence of ILC2s. These data suggest the absence of ILC2s does not alter the severity of renal injury, suggesting possible redundancy. Therefore, other mechanisms of type 2-mediated immune cell activation likely compensate in the absence of ILC2s. Hence, a loss of ILC2s is unlikely to increase susceptibility to, or severity of AKI.

Published
2019

2. The Deubiquitinase OTULIN Is an Essential Negative Regulator of Inflammation and Autoimmunity

Author

Damgaard, Rune Busk, Walker, Jennifer A, Marco-Casanova, Paola, Morgan, Neil V, Titheradge, Hannah L, Elliott, Paul R, McHale, Duncan, Maher, Eamonn R, McKenzie, Andrew NJ, and Komander, David

Subjects
Inflammation, B-Lymphocytes, Deubiquitinating Enzymes, Tumor Necrosis Factor-alpha, T-Lymphocytes, Autoimmunity, Syndrome, Antibodies, Neutralizing, Infliximab, Mice, Mutant Strains, 3. Good health, Autoimmune Diseases, Disease Models, Animal, Mice, Methionine, Endopeptidases, Animals, Cytokines, Humans, Myeloid Cells, Polyubiquitin, Germ-Line Mutation, Sequence Deletion
Abstract

Methionine-1 (M1)-linked ubiquitin chains regulate the activity of NF-κB, immune homeostasis, and responses to infection. The importance of negative regulators of M1-linked chains in vivo remains poorly understood. Here, we show that the M1-specific deubiquitinase OTULIN is essential for preventing TNF-associated systemic inflammation in humans and mice. A homozygous hypomorphic mutation in human OTULIN causes a potentially fatal autoinflammatory condition termed OTULIN-related autoinflammatory syndrome (ORAS). Four independent OTULIN mouse models reveal that OTULIN deficiency in immune cells results in cell-type-specific effects, ranging from over-production of inflammatory cytokines and autoimmunity due to accumulation of M1-linked polyubiquitin and spontaneous NF-κB activation in myeloid cells to downregulation of M1-polyubiquitin signaling by degradation of LUBAC in B and T cells. Remarkably, treatment with anti-TNF neutralizing antibodies ameliorates inflammation in ORAS patients and rescues mouse phenotypes. Hence, OTULIN is critical for restraining life-threatening spontaneous inflammation and maintaining immune homeostasis.

3. A stromal cell niche sustains ILC2-mediated type-2 conditioning in adipose tissue

Author

Meera Sivasubramaniam, Jennifer A. Walker, Antonio Vidal-Puig, Eric Jou, Helle F. Jørgensen, Clare S. Hardman, Jillian L. Barlow, Jorge Caamano, Stefania Carobbio, Sara Cruz Migoni, Matthew Sleeman, Ian C. Scott, Chiamaka I Chidomere, Noé Rodríguez-Rodríguez, Aydan Szeto, Andrew N. J. McKenzie, E. Suzanne Cohen, Batika M. J. Rana, Claire Knox, Helen E. Jolin, Cohen, E Suzanne [0000-0002-4470-1680], Scott, Ian C [0000-0003-4136-4751], Caamano, Jorge [0000-0003-3530-7056], Jorgensen, Helle F [0000-0002-7909-2977], McKenzie, Andrew NJ [0000-0001-9757-2512], and Apollo - University of Cambridge Repository

Subjects
0301 basic medicine, Eotaxin, Stromal cell, medicine.medical_treatment, Adipose Tissue, White, Immunology, Adipose tissue, Biology, 03 medical and health sciences, 0302 clinical medicine, Immune system, medicine, Immunology and Allergy, Humans, Animals, Lymphocytes, Research Articles, Cell Proliferation, Mice, Inbred BALB C, Innate lymphoid cell, Mesenchymal stem cell, Brief Definitive Report, food and beverages, Interleukin-33, Immunity, Innate, Cell biology, Interleukin 33, Eosinophils, Mice, Inbred C57BL, 030104 developmental biology, Cytokine, Adipose Tissue, Diabetes Mellitus, Type 2, Interleukin-5, Stromal Cells, 030215 immunology
Abstract

Rana et al. demonstrate that white adipose tissue-resident multipotent stromal cells (WAT-MSC) support IL-33– and LFA-1/ICAM-1–mediated proliferation and type-2 cytokine expression by ILC2. Inversely, ILC2-derived IL-4 and IL-13 promote WAT-MSC eotaxin production and eosinophil recruitment, further maintaining type-2 immune homeostasis., 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., Graphical Abstract

Published
2020
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