title: Involvement of Ly6C, 4-1BB, and KLRG1 in the activation of lamina propria lymphocytes in the small intestine of sanroque mice.
abstract: Roquin is an E3 ligase that regulates mRNA stability. Mice with a mutation in the Rc3h1 gene and Roquin protein, referred to as Roquinsan/sanor sanroque mice, develop broad-spectrum chronic inflammatory conditions and autoimmune pathologies. Our laboratory recently reported that sanroque mice also develop extensive inflammation that is localized in the small intestine but is rare in the colon. Here, we demonstrate that small intestinal intraepithelial lymphocytes (IELs) are present in the epithelium of sanroque mice but that cell recoverability is low using standard extraction techniques even though lamina propria lymphocytes (LPLs) can be recovered in normal numbers. In studies aimed at characterizing T cell costimulatory markers and activation molecules on LPLs in sanroque mice, we identified Ly6C and 4-1BB (CD137) as being expressed at elevated levels on sanroque small intestinal LPLs, and we show that both of those subsets, in conjunction with cells expressing the KLRG1 T cell activation molecule, are sources of IL-17A, IFN-γ, and TNFα. TNFα was primarily produced by 4-1BB+, KLRG1-cells, but was also made by some 4-1BB-, KLRG1-cells, and 4-1BB-, KLRG1+ cells. These findings collectively suggest that the small intestinal inflammatory response in sanroque mice is driven, at least in part, by LPL activation through Ly6C and 4-1BB signaling, and they provide further evidence in support of using the sanroque mouse as an animal model of chronic small intestinal inflammation.
authors.affiliation: Department of Diagnostic and Biomedical Sciences, School of Dentistry, University of Texas Health Science Center at Houston, Houston TX, USA.
authors.forename: Dina
authors.initials: D
authors.lastname: Montufar-Solis
authors.affiliation: Department of Diagnostic and Biomedical Sciences, School of Dentistry, University of Texas Health Science Center at Houston, Houston TX, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Williams
authors.affiliation: Department of Diagnostic and Biomedical Sciences, School of Dentistry, University of Texas Health Science Center at Houston, Houston TX, USA.
authors.forename: Nadarajah
authors.initials: N
authors.lastname: Vigneswaran
authors.affiliation: Department of Diagnostic and Biomedical Sciences, School of Dentistry, University of Texas Health Science Center at Houston, Houston TX, USA. Electronic address: john.r.klein@uth.tmc.edu.
authors.forename: John R
authors.initials: JR
authors.lastname: Klein
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000502:physiology*; D003424:Crohn Disease / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006579:Heterozygote; D007249:Inflammation; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D007421:Intestine, Small / Q000378:metabolism; D037181:Lectins, C-Type; D008214:Lymphocytes / Q000378:metabolism*; D051379:Mice; D009092:Mucous Membrane / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000502:physiology*; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000950:Antigens, Ly; C000611649:IFNG protein, mouse; D020381:Interleukin-17; C451496:Klrg1 protein, mouse; D037181:Lectins, C-Type; C494192:Ly-6C antigen, mouse; D011971:Receptors, Immunologic; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma
keywords: Costimulation; Inflammation; Intestine; Proinflammatory cytokine; Roquin