Infection and inflammation stimulate expansion of a CD74 + Paneth cell subset to regulate disease progression.

Autor: Balasubramanian I; Department of Biological Sciences, Rutgers University, Newark, NJ, USA., Bandyopadhyay S; Department of Biological Sciences, Rutgers University, Newark, NJ, USA., Flores J; Department of Biological Sciences, Rutgers University, Newark, NJ, USA., Bianchi-Smak J; Department of Biological Sciences, Rutgers University, Newark, NJ, USA., Lin X; Department of Computer Science, New Jersey Institute of Technology, Newark, NJ, USA., Liu H; Department of Computer Science, New Jersey Institute of Technology, Newark, NJ, USA., Sun S; Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO, USA., Golovchenko NB; Center for Immunity and Inflammation, Rutgers New Jersey Medical School, Newark, NJ, USA., Liu Y; Department of Biological Sciences, Rutgers University, Newark, NJ, USA., Wang D; Department of Biological Sciences, Rutgers University, Newark, NJ, USA., Patel R; Department of Biological Sciences, Rutgers University, Newark, NJ, USA., Joseph I; Department of Biological Sciences, Rutgers University, Newark, NJ, USA., Suntornsaratoon P; Department of Pharmacology, Physiology & Neuroscience, Rutgers New Jersey Medical School, Newark, NJ, USA., Vargas J; Department of Medicine, Celiac Disease Center, Columbia University Irving Medical Center, New York, NY, USA., Green PH; Department of Medicine, Celiac Disease Center, Columbia University Irving Medical Center, New York, NY, USA., Bhagat G; Department of Medicine, Celiac Disease Center, Columbia University Irving Medical Center, New York, NY, USA.; Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USA., Lagana SM; Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USA., Ying W; Hackensack Meridian Health Center for Discovery and Innovation, Nutley, NJ, USA., Zhang Y; Hackensack Meridian Health Center for Discovery and Innovation, Nutley, NJ, USA., Wang Z; Department of Statistics, Rutgers University, New Brunswick, NJ, USA., Li WV; Department of Biostatistics and Epidemiology, Rutgers University, New Brunswick, NJ, USA., Singh S; Department of Pathology, Rutgers New Jersey Medical School, Newark, NJ, USA., Zhou Z; Department of Pathology & Laboratory Medicine, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ, USA., Kollias G; Biomedical Sciences Research Centre, 'Alexander Fleming', Vari, Greece., Farr LA; Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, USA., Moonah SN; Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, USA., Yu S; Department of Biological Sciences, Rutgers University, Newark, NJ, USA., Wei Z; Department of Computer Science, New Jersey Institute of Technology, Newark, NJ, USA., Bonder EM; Department of Biological Sciences, Rutgers University, Newark, NJ, USA., Zhang L; Department of Biological Sciences, Rutgers University, Newark, NJ, USA.; Department of Pathology, Penn Medicine Princeton Medical Center, Plainsboro, NJ, USA., Kiela PR; Departments of Pediatrics and Immunology, and Daniel Cracchiolo Institute for Pediatric Autoimmune Disease Research, Steele Children's Research Center, The University of Arizona Health Sciences, Tucson, AZ, USA., Edelblum KL; Center for Immunity and Inflammation, Rutgers New Jersey Medical School, Newark, NJ, USA., Ferraris R; Department of Pharmacology, Physiology & Neuroscience, Rutgers New Jersey Medical School, Newark, NJ, USA., Liu TC; Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO, USA., Gao N; Department of Biological Sciences, Rutgers University, Newark, NJ, USA.
Jazyk: angličtina
Zdroj: The EMBO journal [EMBO J] 2023 Nov 02; Vol. 42 (21), pp. e113975. Date of Electronic Publication: 2023 Sep 18.
DOI: 10.15252/embj.2023113975
Abstrakt: Paneth cells (PCs), a specialized secretory cell type in the small intestine, are increasingly recognized as having an essential role in host responses to microbiome and environmental stresses. Whether and how commensal and pathogenic microbes modify PC composition to modulate inflammation remain unclear. Using newly developed PC-reporter mice under conventional and gnotobiotic conditions, we determined PC transcriptomic heterogeneity in response to commensal and invasive microbes at single cell level. Infection expands the pool of CD74 + PCs, whose number correlates with auto or allogeneic inflammatory disease progressions in mice. Similar correlation was found in human inflammatory disease tissues. Infection-stimulated cytokines increase production of reactive oxygen species (ROS) and expression of a PC-specific mucosal pentraxin (Mptx2) in activated PCs. A PC-specific ablation of MyD88 reduced CD74 + PC population, thus ameliorating pathogen-induced systemic disease. A similar phenotype was also observed in mice lacking Mptx2. Thus, infection stimulates expansion of a PC subset that influences disease progression.
(© 2023 The Authors. Published under the terms of the CC BY NC ND 4.0 license.)
Databáze: MEDLINE
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