BTNL2, a Butyrophilin/B7-like molecule, is a negative co-stimulatory molecule modulated in intestinal inflammation
Abstract
BTNL2, a Butyrophilin/B7-Like Molecule, Is a Negative Costimulatory Molecule Modulated in Intestinal Inflammation Heather A. Arnett,1* Sabine S. Escobar,1* Eva Gonzalez-Suarez,* Alison L. Budelsky,* Lori A. Steffen,* Norman Boiani,† Ming Zhang,§ Gerald Siu,§ Avery W. Brewer,‡ and Joanne L. Viney2* Butyrophilin-like 2 (BTNL2) is a butyrophilin family member with homology to the B7 costimulatory molecules, polymorphisms of which have been recently associated through genetic analyses to sporadic inclusion body myositis and sarcoidosis. We have characterized the full structure, expression, and function of BTNL2. Structural analysis of BTNL2 shows a molecule with an extracellular region containing two sets of two Ig domains, a transmembrane region, and a previously unreported cytoplasmic tail. Unlike most other butyrophilin members, BTNL2 lacks the prototypical B30.2 ring domain. TaqMan and Northern blot analysis indicate BTNL2 is predominantly expressed in digestive tract tissues, in particular small intestine and Peyer’s patches. Immunohisto- chemistry with BTNL2-specific Abs further localizes BTNL2 to epithelial and dendritic cells within these tissues. Despite its homology to the B7 family, BTNL2 does not bind any of the known B7 family receptors such as CD28, CTLA-4, PD-1, ICOS, or B and T lymphocyte attenuator. Because of its localization in the gut and potential role in the immune system, BTNL2 expression was analyzed in a mouse model of inflammatory bowel disease. BTNL2 is overexpressed during both the asymptomatic and symptomatic phase of the Mdr1a knockout model of spontaneous colitis. In functional assays, soluble BTNL2-Fc protein inhibits the proliferation of murine CD4 T cells from the spleen, mesenteric lymph node, and Peyer’s patch. In addition, BTNL2-Fc reduces proliferation and cytokine produc- tion from T cells activated by anti-CD3 and B7-related protein 1. These data suggest a role for BTNL2 as a negative costimulatory molecule with implications for infl
Key Biomarkers
Symptom Clusters
Cited By (6)
- Confirmation of the novel association at the BTNL2 locus with ulcerative colitisTissue Antigens · 2009
- The BTNL2 A allele variant is frequent in Danish patients with sarcoidosisThe Clinical Respiratory Journal · 2011
- Stimulation of human butyrophilin 3 molecules results in negative regulation of cellular immunityJournal of Leukocyte Biology · 2010
- Butyrophilin-like 2 in pulmonary sarcoidosis: a factor for susceptibility and progression?Human Immunology · 2011
- The B7 Homolog Butyrophilin BTN2A1 Is a Novel Ligand for DC-SIGNThe Journal of Immunology · 2007
- Regulation of co-stimulation in the era of butyrophilinsCytokine · 2009
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