title: CD8αα⁺ innate-type lymphocytes in the intestinal epithelium mediate mucosal immunity.
abstract: Innate immune responses are critical for mucosal immunity. Here we describe an innate lymphocyte population, iCD8α cells, characterized by expression of CD8α homodimers. iCD8α cells exhibit innate functional characteristics such as the capacity to engulf and kill bacteria. Development of iCD8α cells depends on expression of interleukin-2 receptor γ chain (IL-2Rγc), IL-15, and the major histocompatibility complex (MHC) class Ib protein H2-T3, also known as the thymus leukemia antigen or TL. While lineage tracking experiments indicated that iCD8α cells have a lymphoid origin, their development was independent of the transcriptional suppressor Id2, suggesting that these cells do not belong to the family of innate lymphoid cells. Finally, we identified cells with a similar phenotype in humans, which were profoundly depleted in newborns with necrotizing enterocolitis. These findings suggest a critical role of iCD8α cells in immune responses associated with the intestinal epithelium.
authors.affiliation: Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA. Electronic address: luc.van.kaer@vanderbilt.edu.
authors.forename: Luc
authors.initials: L
authors.lastname: Van Kaer
authors.affiliation: Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA; Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN 37232, USA; Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors.forename: Holly M Scott
authors.initials: HMS
authors.lastname: Algood
authors.affiliation: Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors.forename: Kshipra
authors.initials: K
authors.lastname: Singh
authors.affiliation: Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors.forename: Vrajesh V
authors.initials: VV
authors.lastname: Parekh
authors.affiliation: Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Greer
authors.affiliation: Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors.forename: M Blanca
authors.initials: MB
authors.lastname: Piazuelo
authors.affiliation: Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors.forename: Jörn-Hendrik
authors.initials: JH
authors.lastname: Weitkamp
authors.affiliation: Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors.forename: Pranathi
authors.initials: P
authors.lastname: Matta
authors.affiliation: Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors.forename: Rupesh
authors.initials: R
authors.lastname: Chaturvedi
authors.affiliation: Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA; Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN 37232, USA; Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA; Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors.forename: Keith T
authors.initials: KT
authors.lastname: Wilson
authors.affiliation: Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA. Electronic address: danyvid.olivares-villagomez@vanderbilt.edu.
authors.forename: Danyvid
authors.initials: D
authors.lastname: Olivares-Villagómez
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D016827:CD8 Antigens / Q000096:biosynthesis*; D044082:Citrobacter rodentium / Q000276:immunology; D015638:Cytochalasin D / Q000494:pharmacology; D020345:Enterocolitis, Necrotizing; D016480:Helicobacter pylori / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis; D006801:Humans; D018928:Immunity, Mucosal / Q000276:immunology*; D051797:Inhibitor of Differentiation Protein 2 / Q000235:genetics; D053631:Interleukin Receptor Common gamma Subunit / Q000096:biosynthesis; D019409:Interleukin-15 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D015851:Interleukin-7 / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000166:cytology* / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008214:Lymphocytes / Q000145:classification / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology
chemical_list: D016827:CD8 Antigens; C409469:CD8 antigen, alpha chain; D015395:Histocompatibility Antigens Class I; C497452:Idb2 protein, mouse; D051797:Inhibitor of Differentiation Protein 2; D053631:Interleukin Receptor Common gamma Subunit; D019409:Interleukin-15; D007376:Interleukin-2; D015851:Interleukin-7; C098080:MICB antigen; D015638:Cytochalasin D