Progressive accumulation of hyperinflammatory NKG2D low NK cells in early childhood severe atopic dermatitis.

Autor: Ochayon DE; Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.; Division of Asthma Research, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA., DeVore SB; Division of Asthma Research, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.; Medical Scientist Training Program, University of Cincinnati College of Medicine, Cincinnati, OH, USA.; Cancer and Cell Biology Program, University of Cincinnati College of Medicine, Cincinnati, OH, USA., Chang WC; Division of Asthma Research, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA., Krishnamurthy D; Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.; Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA., Seelamneni H; Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.; Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA., Grashel B; Division of Asthma Research, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA., Spagna D; Division of Asthma Research, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA., Andorf S; Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.; Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.; Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA., Martin LJ; Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.; Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA., Biagini JM; Division of Asthma Research, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA., Waggoner SN; Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.; Medical Scientist Training Program, University of Cincinnati College of Medicine, Cincinnati, OH, USA.; Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA., Khurana Hershey GK; Division of Asthma Research, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.; Medical Scientist Training Program, University of Cincinnati College of Medicine, Cincinnati, OH, USA.; Cancer and Cell Biology Program, University of Cincinnati College of Medicine, Cincinnati, OH, USA.; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Jazyk: angličtina
Zdroj: Science immunology [Sci Immunol] 2024 Sep 02; Vol. 9 (92), pp. eadd3085. Date of Electronic Publication: 2024 Feb 09.
DOI: 10.1126/sciimmunol.add3085
Abstrakt: Atopic dermatitis (AD) is a chronic inflammatory skin disease that often precedes the development of food allergy, asthma, and allergic rhinitis. The prevailing paradigm holds that a reduced frequency and function of natural killer (NK) cell contributes to AD pathogenesis, yet the underlying mechanisms and contributions of NK cells to allergic comorbidities remain ill-defined. Here, analysis of circulating NK cells in a longitudinal early life cohort of children with AD revealed a progressive accumulation of NK cells with low expression of the activating receptor NKG2D, which was linked to more severe AD and sensitivity to allergens. This was most notable in children co-sensitized to food and aeroallergens, a risk factor for development of asthma. Individual-level longitudinal analysis in a subset of children revealed coincident reduction of NKG2D on NK cells with acquired or persistent sensitization, and this was associated with impaired skin barrier function assessed by transepidermal water loss. Low expression of NKG2D on NK cells was paradoxically associated with depressed cytolytic function but exaggerated release of the proinflammatory cytokine tumor necrosis factor-α. These observations provide important insights into a potential mechanism underlying the development of allergic comorbidity in early life in children with AD, which involves altered NK cell functional responses, and define an endotype of severe AD.
Databáze: MEDLINE