BACKGROUND & AIMS: Innate and adaptive immune responses are regulated by cross talk between activation and inhibitory signals. Dysregulation of the inhibitory signal can lead to aberrant chronic inflammatory diseases such as the inflammatory bowel diseases (IBD). Little is known about negative regulation of innate intestinal immune activation. We examined the role of the inhibitory receptor paired immunoglobulin-like receptor B (PIR-B) in the regulation of macrophage function in innate intestinal immunity. METHODS: We examined the susceptibility of Pirb-/- and wild-type (WT) mice to dextran sodium sulfate (DSS)-induced colitis. We assessed proinflammatory cytokine release and mitogen-activated protein kinase (MAPK) and nuclear factor kappaB (NF-kappaB) activation in Pirb-/- and WT macrophages following Escherichia coli stimulation. Macrophage transfer experiments were performed to define the role of PIR-B in the negative regulation of macrophage function in DSS-induced colitis. We also assessed expression of PIR-B human homologues (immunoglobulin-like transcript [ILT]-2 and ILT-3) in colon biopsy samples from healthy individuals (controls) and patients with IBD. RESULTS: Pirb-/- mice had increased susceptibility to DSS-induced colitis. In vitro analysis showed increased production of proinflammatory cytokines (interleukin-6, interleukin-1beta, and tumor necrosis factor alpha) and activation of MAPK and NF-kappaB in Pirb-/- macrophages following bacterial activation. Adoptive transfer of bone marrow-derived Pirb-/- macrophages into WT mice was sufficient to increase disease susceptibility. ILT-2 and ILT-3 were expressed on CD68+ and CD68- mononuclear cells and intestinal epithelium in colon biopsy samples from patients and controls. CONCLUSIONS: PIR-B negatively regulates macrophage functions in response to pathogenic bacteria and chronic intestinal inflammatory responses. Inhibitory receptors such as PIR-B might be used as therapeutic targets for treatment of patients with IBD. Copyright (c) 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.
BACKGROUND & AIMS: Innate and adaptive immune responses are regulated by cross talk between activation and inhibitory signals. Dysregulation of the inhibitory signal can lead to aberrant chronic inflammatory diseases such as the inflammatory bowel diseases (IBD). Little is known about negative regulation of innate intestinal immune activation. We examined the role of the inhibitory receptor paired immunoglobulin-like receptor B (PIR-B) in the regulation of macrophage function in innate intestinal immunity. METHODS: We examined the susceptibility of Pirb-/- and wild-type (WT) mice to dextran sodium sulfate (DSS)-induced colitis. We assessed proinflammatory cytokine release and mitogen-activated protein kinase (MAPK) and nuclear factor kappaB (NF-kappaB) activation in Pirb-/- and WT macrophages following Escherichia coli stimulation. Macrophage transfer experiments were performed to define the role of PIR-B in the negative regulation of macrophage function in DSS-induced colitis. We also assessed expression of PIR-Bhuman homologues (immunoglobulin-like transcript [ILT]-2 and ILT-3) in colon biopsy samples from healthy individuals (controls) and patients with IBD. RESULTS:Pirb-/- mice had increased susceptibility to DSS-induced colitis. In vitro analysis showed increased production of proinflammatory cytokines (interleukin-6, interleukin-1beta, and tumor necrosis factor alpha) and activation of MAPK and NF-kappaB in Pirb-/- macrophages following bacterial activation. Adoptive transfer of bone marrow-derived Pirb-/- macrophages into WT mice was sufficient to increase disease susceptibility. ILT-2 and ILT-3 were expressed on CD68+ and CD68- mononuclear cells and intestinal epithelium in colon biopsy samples from patients and controls. CONCLUSIONS:PIR-B negatively regulates macrophage functions in response to pathogenic bacteria and chronic intestinal inflammatory responses. Inhibitory receptors such as PIR-B might be used as therapeutic targets for treatment of patients with IBD. Copyright (c) 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.
Authors: Nicodemus Tedla; Kathryn Gibson; H Patrick McNeil; David Cosman; Luis Borges; Jonathan P Arm Journal: Am J Pathol Date: 2002-02 Impact factor: 4.307
Authors: C F Krieglstein; W H Cerwinka; F S Laroux; J W Salter; J M Russell; G Schuermann; M B Grisham; C R Ross; D N Granger Journal: J Exp Med Date: 2001-11-05 Impact factor: 14.307
Authors: Amanda Waddell; Richard Ahrens; Kris Steinbrecher; Burke Donovan; Marc E Rothenberg; Ariel Munitz; Simon P Hogan Journal: J Immunol Date: 2011-04-15 Impact factor: 5.422
Authors: Clara Meana; Ginesa García-Rostán; Lucía Peña; Gema Lordén; África Cubero; Antonio Orduña; Balázs Győrffy; Jesús Balsinde; María A Balboa Journal: JCI Insight Date: 2018-09-20
Authors: Sandra Pinho; Qiaozhi Wei; Maria Maryanovich; Dachuan Zhang; Juan Carlos Balandrán; Halley Pierce; Fumio Nakahara; Anna Di Staulo; Boris A Bartholdy; Jianing Xu; Daniel K Borger; Amit Verma; Paul S Frenette Journal: Nat Cell Biol Date: 2022-02-24 Impact factor: 28.213