Review
Why does chronic inflammation persist: An unexpected role for fibroblasts

https://doi.org/10.1016/j.imlet.2011.02.010Get rights and content

Abstract

One of the most important but as yet unanswered questions in inflammation research is not why inflammation occurs (we all get episodes of self limiting inflammation during the course of our lives) 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 leukocyte and have instead focused on an extended immune system in which stromal cells, such as fibroblasts play a role in the persistence of the inflammatory lesion.

In this review I will illustrate how fibroblasts help regulate the switch from acute resolving to chronic persistent inflammation and provide positional memory during inflammatory responses. In chronic inflammation the normal physiological process of the removal of unwanted inflammatory effector cells becomes disordered, leading to the accumulation of leucocytes within lymphoid aggregates that resemble those seen in lymphoid tissue. I will describe how fibroblasts provide survival and retention signals for leukocytes leading to their inappropriate and persistent accumulation within inflamed tissue.

Section snippets

Background

Two characteristic features of chronic inflammatory reactions are their persistence and predilection for certain sites. Why for example do some forms of inflammation resolve, yet others do not? Why does arthritis localize predominantly to the joints compared to psoriasis which localizes predominantly to the skin? It has been assumed that inflammation is a stereotyped response that reflects a common or “public” set of shared pathways leading to endothelial cell activation, leukocyte infiltration

Concluding remarks

Immune cells need to interact with a wide variety of cell types both within immune (lymphoid) and peripheral tissues. During inflammation, stromal cells such as fibroblasts, become activated and interact with infiltrating immune cells in a dynamic and site-specific manner. Populations of leukocytes recruited to sites of inflammation should not be considered in isolation, but in conjunction with the non-immune cells that help provide survival, differentiation and positional cues upon which the

References (15)

  • C.D. Buckley et al.

    Trends Immunol

    (2001)
  • G. Parsonage et al.

    Trends Immunol

    (2005)
  • D. Pilling et al.

    Eur J Immunol

    (1999)
  • C.D. Buckley et al.

    J Immunol

    (2000)
  • N. Amft et al.

    Arthritis Rheum

    (2001)
  • P.F. Bradfield et al.

    Arthritis Rheum

    (2003)
  • C.D. Buckley

    Rheumatology

    (2003)
There are more references available in the full text version of this article.

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