A characteristic feature of chronic inflammatory reactions is their persistence and predilection for certain sites. Our group investigates the role that tissue resident stromal cells (fibroblasts) play in determining both the switch to persistence as well as the site at which inflammation occurs. In chronic inflammation the resolution phase is prolonged and disordered leading to the persistent accumulation of the inflammatory infiltrate. Our work has allowed us to propose that a stromal area post code, predominantly defined by fibroblasts, exists within tissues. Our hypothesis predicts that components of this stromal area post code become disordered during inflammation, leading to the accumulation of lymphocytes in structures that resemble lymphoid tissues. We have proposed that inflammation is not generic but contextual and therefore differences in the response of different inflammatory diseases to therapy are likely to be due to intrinsic differences in the behavior of stromal cells within different environments. Ignoring the contribution of stromal cells to the pathogenesis of chronic inflammatory disease may account for the failure of current therapies to affect a permanent cure. We suggest that stromal cells in general and fibroblasts in particular offer a new family of organ specific targets to treat chronic immune mediated inflammatory diseases such as rheumatoid arthritis
For more information about Chris Buckley's research follow the links below:
BBC Radio 4 (2004) Inflammation
BBC Radio 4 (2008) Inflamed Response
Association of T-zone reticular networks and conduits with ectopic lymphoid tissues in mice and humans.Link A, Hardie DL, Favre S, Britschgi MR, Adams DH, Sixt M, Cyster JG, Buckley CD, Luther SA.Am J Pathol. 2011 Apr;178(4):1662-75.
Why does chronic inflammation persist: An unexpected role for fibroblasts.Buckley CD.Immunol Lett. 2011 Feb 17. [Epub ahead of print] Performance of the 2010 ACR/EULAR criteria for rheumatoid arthritis: comparison with 1987 ACR criteria in a very early synovitis cohort.
Cader MZ, Filer A, Hazlehurst J, de Pablo P, Buckley CD, Karim R.Ann Rheum Dis. 2011 Feb 1. [Epub ahead of print]PMID: 21285117
Altered expression of microRNA-203 in rheumatoid arthritis synovial fibroblasts and its role in fibroblast activation.Stanczyk J, Ospelt C, Karouzakis E, Filer A, Raza K, Kolling C, Gay R, Buckley CD, Tak PP, Gay S, Kyburz D.Arthritis Rheum. 2011 Feb;63(2):373-81. doi: 10.1002/art.30115.
Utility of ultrasound joint counts in the prediction of rheumatoid arthritis in patients with very early synovitis.Filer A, de Pablo P, Allen G, Nightingale P, Jordan A, Jobanputra P, Bowman S, Buckley CD, Raza K.Ann Rheum Dis. 2011 Mar;70(3):500-7. Epub 2010 Nov 29.
Genome-wide association study of genetic predictors of anti-tumor necrosis factor treatment efficacy in rheumatoid arthritis identifies associations with polymorphisms at seven loci.Plant D, Bowes J, Potter C, Hyrich KL, Morgan AW, Wilson AG, Isaacs JD; Wellcome Trust Case Control Consortium; British Society for Rheumatology Biologics Register, Barton A.Arthritis Rheum. 2011 Mar;63(3):645-53. doi: 10.1002/art.30130.
Rheumatoid synovial fluid interleukin-17-producing CD4 T cells have abundant tumor necrosis factor-alpha co-expression, but little interleukin-22 and interleukin-23R expression.Church LD, Filer AD, Hidalgo E, Howlett KA, Thomas AM, Rapecki S, Scheel-Toellner D, Buckley CD, Raza K.Arthritis Res Ther. 2010;12(5):R184. Epub 2010 Oct
Monocytes/macrophages express chemokine receptor CCR9 in rheumatoid arthritis and CCL25 stimulates their differentiation.Schmutz C, Cartwright A, Williams H, Haworth O, Williams JH, Filer A, Salmon M, Buckley CD, Middleton J.Arthritis Res Ther. 2010;12(4):R161. Epub 2010 Aug 25.