Trends in Immunology
OpinionFibroblasts regulate the switch from acute resolving to chronic persistent inflammation
Section snippets
Not all fibroblasts are the same
Fibroblasts are ubiquitous cells that provide mechanical strength to tissues by providing a supporting framework of ECM (Refs 10,11). However, not all fibroblasts are the same. For example, although most fibroblasts are classically thought to be mesodermal in origin, fibroblasts in the head and neck region are derived from neural crest tissue (i.e. ectodermal in origin) 11, 12. Recent studies have shown that thymic fibroblasts play an important role in early T-cell development. This provides an
Fibroblast activation and chronic inflammation
Until recently, the activation of fibroblasts was thought to lead to a relatively restricted biosynthetic repertoire. It is now clear that fibroblast activation leads to the rapid production of cytokines, chemokines and prostanoids such as PGE2. In addition, fibroblasts regulate the behaviour of haematopoietic cells that infiltrate damaged tissue through CD40–CD40 ligand (L) interactions 20. The engagement of CD40 on fibroblasts from a diverse range of tissues leads to the activation of the
The dynamics of an inflammatory infiltrate
Inflammatory responses take place within tissue microenvironments. Such environments are complex and are composed of many different cell types that are often at different stages of activation and differentiation 4. Although the mechanisms responsible for the recruitment and migration of peripheral blood leukocytes into sites of inflammation are well studied, those responsible for the persistence of inflammatory cells within chronically inflamed tissue have attracted much less attention (Fig. 2
Chronically inflammed tissue is highly stable
Chronic inflammation is not synonymous with chronic infection. Although infectious agents such as parasites, bacteria and viruses are important danger signals for the immune system, many other injurious stimuli such as trauma and even some cancers are not antigen specific but still lead to an inflammatory response. Chemokines secreted by fibroblasts are an important link between the innate and acquired immune responses and play a crucial role in determining the nature and magnitude of the
Chronic inflammatory microenvironments: ‘foster homes’ for leukocytes?
The transition from an acute inflammatory response to acquired immunity is a vulnerable time for the immune system. In order to generate an efficient adaptive immune response to antigen, immature dendritic cells must sample antigen within inflamed tissue and then migrate to the draining lymph node where they present antigen to T cells. This process is spatially separated from the site of inflammation and requires careful chemokine-mediated choreography in order for the appropriate immune cells
Conclusions
The immune system is a diverse collection of many cell types that are spatially and temporally separated from each other. In order for efficient immune responses to occur, cells of the innate and acquired immune system must interact with each other. They do this both through the release of soluble mediators and through direct cell–cell contact. An emerging theme in recent years is that cells of mesenchymal origin, such as fibroblasts, play a critical role in modulating leukocyte behaviour and
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