Defining a role for fibroblasts in the persistence of chronic inflammatory joint disease

  • C Buckley1,

    Affiliated with

    • A Filer1,

      Affiliated with

      • O Haworth1,

        Affiliated with

        • G Parsonage1,

          Affiliated with

          • K Raza1 and

            Affiliated with

            • M Salmon1

              Affiliated with

              Arthritis Research & Therapy20057(Suppl 1):S14

              DOI: 10.1186/ar1512

              Received: 11 January 2005

              Published: 17 February 2005

              One of the most important but as yet unanswered questions in inflammation research is not why chronic inflammation occurs but why it does not resolve. Current models of inflammation stress the role of antigen-specific lymphocyte responses and attempt to address the causative agent. However, recent studies have begun to challenge the primacy of the lymphocyte and have begun to focus on an extended immune system in which stromal cells, such as macrophages and fibroblasts, play a role in the persistence of the inflammatory lesion.

              In this lecture I will illustrate how fibroblasts play an important role in regulating the switch from acute resolving to chronic persistent inflammation associated with the pathology of diseases such as rheumatoid arthritis [1]. In chronic inflammation the normal physiological process of the death and emigration of unwanted inflammatory effector cells becomes disordered leading to accumulation of leucocytes [24] within lymphoid aggregates that resemble those seen in lymphoid tissue [5]. I will describe how fibroblasts from the rheumatoid joint provide survival and retention signals for leucocytes leading to their inappropriate and persistent accumulation within inflamed tissue [6]. Our work suggests that targeting the stromal microenvironment is likely to be an important strategy for future anti-inflammatory therapies.

              Authors’ Affiliations

              (1)
              Rheumatology Research Group, Division of Immunity and Infection, MRC Centre for Immune Regulation, The University of Birmingham

              References

              1. Buckley CD, Pilling D, Lord JM, Akbar AN, Scheel-Toellner D, Salmon M: Fibroblasts regulate the switch from acute resolving to chronic persistent inflammation. Trends Immunol 2001, 22:199–204.View ArticlePubMed
              2. Salmon M, Scheel-Toellner D, Huissoon AP, Pilling D, Shamsadeen N, Hyde H, D'Angeac AD, Bacon PA, Emery P, Akbar AN: Inhibition of T cell apoptosis in the rheumatoid synovium. J Clin Invest 1997, 99:439–446.View ArticlePubMed
              3. Buckley CD, Amft N, Bradfield PF, Pilling D, Ross E, Arenzana-Seisdedos F, Amara A, Curnow SJ, Lord JM, Scheel-Toellner D, Salmon M: Persistent induction of the chemokine receptor CXCR4 by TGF-beta 1 on synovial T cells contributes to their accumulation within the rheumatoid synovium. J Immunol 2000, 165:3423–3429.PubMed
              4. Buckley CD: Why do leucocytes accumulate within chronically inflamed joints? Rheumatology 2003, 42:1433–1444.View ArticlePubMed
              5. Amft N, Curnow SJ, Scheel-Toellner D, Devadas A, Oates J, Crocker J, Hamburger J, Ainsworth J, Mathews J, Salmon M, et al.: Ectopic expression of the B cell attracting chemokine BCA-1 (CXCL13) on endothelial cells and within lymphoid follicles contributes to the establishment of germinal center-like structures in Sjögren's Syndrome. Arthritis Rheum 2001, 44:2633–2641.View ArticlePubMed
              6. Parsonage G, Falciani F, Burman A, Filer A, Ross E, Bofill M, Martin S, Salmon M, Buckley CD: Global gene expression profiles in fibroblasts from synovial, skin and lymphoid tissue reveals distinct cytokine and chemokine expression patterns. Thromb Haemost 2003, 90:688–697.PubMed

              Copyright

              © BioMed Central Ltd 2005

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