Animal models of HLA-B27-associated diseases: new outcomes.
The HLA-B27 molecule is strongly associated with the spondyloarthropathies, a group of chronic inflammatory diseases, affecting the skeleton, the bowel and the skin. This association has been largely studied, but mechanisms of pathology remain unclear. The HLA-B27 transgenic rats develop a spontaneous disease that strikingly resembles human spondyloarthropathies, dependent of bacterial flora and implicating the immune system. The presence of CD4+ T cells is required, and antigen presenting cells (APC) expressing high levels of HLA-B27 likely play an important role. Indeed, APC are defective in naive T lymphocytes stimulation. This default appears to implicate the APC/T cells contact, and may result in a loss of tolerance toward microbial flora. Two models of skeletal inflammation linked to HLA-B27 have been developed in mice. The ANKENT mice develop a spontaneous ossifying enthesitis affecting ankle and tarsal joints, with increased frequency in the presence of an HLA-B27 transgene. The HLA-B27 transgenic mice lacking endogenous beta2 microglobulin develop arthritis of hind-paws. In this model, homodimers of B27 heavy chains could be implicated in the pathogenesis by presenting exogenous peptides to CD4+ T cells.
Hacquard-Bouder
Cécile
C
Institut Cochin, Inserm U567/CNRS UMR8104/IFR116, hôpital Cochin, 27, rue du Faubourg Saint-Jacques 75014 Paris, France. hacquard@cochin.inserm.fr
Ittah
Marc
M
Breban
Maxime
M
D000818:Animals; D030801:Animals, Genetically Modified; D004195:Disease Models, Animal; D015796:HLA-B27 Antigen / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D051381:Rats; D011919:Rats, Inbred Strains / Q000235:genetics; D025242:Spondylarthropathies / Q000235:genetics* / Q000276:immunology*
D015796:HLA-B27 Antigen