| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Inflammation,
Protein Sciences, and
Pathology, Amgen, Seattle, WA 98119; and
Inflammation, Amgen, Thousand Oaks, CA 91320
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. Immunohistochemistry 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 production 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 inflammatory disease.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 H.A.A. and S.S.E. contributed equally to this work.
2 Address correspondence and reprint requests to Dr. Joanne L. Viney, Department of Inflammation, Amgen, 1201 Amgen Court West, Seattle, WA 98119. E-mail address: vineyj{at}amgen.com
3 Abbreviations used in this paper: B7RP1, B7-related protein 1; BTLA, B and T lymphocyte attenuator; BTNL, butyrophilin-like; MLN, mesenteric lymph node; PP, Peyer’s patch; CHO, Chinese hamster ovary.
This article has been cited by other articles:
|
|
 |
|
  International MHC and Autoimmunity Genetics Networ, J. D. Rioux, P. Goyette, T. J. Vyse, L. Hammarstrom, M. M. A. Fernando, T. Green, P. L. De Jager, S. Foisy, J. Wang, et al. Mapping of multiple susceptibility variants within the MHC region for 7 immune-mediated diseases PNAS, November 3, 2009; 106(44): 18680 - 18685. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Jeong, A. U. Rao, J. Xu, S. L. Ogg, Y. Hathout, C. Fenselau, and I. H. Mather The PRY/SPRY/B30.2 Domain of Butyrophilin 1A1 (BTN1A1) Binds to Xanthine Oxidoreductase: IMPLICATIONS FOR THE FUNCTION OF BTN1A1 IN THE MAMMARY GLAND AND OTHER TISSUES J. Biol. Chem., August 14, 2009; 284(33): 22444 - 22456. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. Iannuzzi, B. A. Rybicki, and A. S. Teirstein Sarcoidosis N. Engl. J. Med., November 22, 2007; 357(21): 2153 - 2165. [Full Text] [PDF]
|
|
|
|
 |
|
 G. Malcherek, L. Mayr, P. Roda-Navarro, D. Rhodes, N. Miller, and J. Trowsdale The B7 Homolog Butyrophilin BTN2A1 Is a Novel Ligand for DC-SIGN J. Immunol., September 15, 2007; 179(6): 3804 - 3811. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Shiina, W. E. Briles, R. M. Goto, K. Hosomichi, K. Yanagiya, S. Shimizu, H. Inoko, and M. M. Miller Extended Gene Map Reveals Tripartite Motif, C-Type Lectin, and Ig Superfamily Type Genes within a Subregion of the Chicken MHC-B Affecting Infectious Disease J. Immunol., June 1, 2007; 178(11): 7162 - 7172. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
