Description
The close anatomic juxtaposition of epithelial cells with lymphocytes lining the intestinal tract facilitates communication between the two cell types. This intercellular dialogue is important for mucosal development and has a conditioning effect on mucosal structure, function, and response to tissue injury. Lymphoepithelial communication is bi-directional, and mediated in large part, by shared ligands and receptors. The chemical messengers involved include cytokines, growth factors, local hormones, and products of arachidonate metabolism. The interdependency between the epithelium and adjacent lymphoid cells is such that the epithelium is considered to have a central role in the mucosa} immune system and is an active participant in both the afferent and efferent limbs of the mucosal immune response. The molecular crosstalk between the epithelium and adjacent lymphocytes is-just one aspect of a more complex network of intercellular signalling within the intestinal mucosa and upon which the integrity of the mucosa is dependent. Thus, there are extensive interactions between nerve and immune cells and between the enteric flora and the epithelium and amongst intestinal mesenchymal cells including fibroblasts and vascular endothelial cells. Disruption of any aspect of the mucosal microenvironment, as has been achieved with selective genetically engineered murine models, is associated with impaired mucosal defence and inflammation.
INTRODUCTION
The notion that different cell-types juxtaposed within a specialised tissue might communicate with one another seems intuitively self-evident, but the extent of lymphoepithelial interactions within the gastrointestinal mucosa has only recently become apparent. The purpose of this brief overview is to present a perspective on integrative immunoepithelial physiology in health and disease. Recent reports are emphasised; more comprehensive analysis including details of earlier studies have been reviewed elsewhere (Castro, 1982; Befus, 1990; Castro and Arntzen, 1993; Perdue and McKay, 1994; Shanahan, 1994; Stenson and Alpers, 1994).
The intestinal epithelium in health and disease is engaged in continual dialogue with neighbouring lymphoid cells both above and below the basement membrane. Only a single layer of cells above the basement membrane separates the external environment ( enteric lumen) from the internal milieu. Within this layer, the intraepithelial lymphocytes (IELs) account for approximately ten percent of the cells and collectively represent a significant lymphoid mass, which in aggregate, would approximate to the size of the spleen (Brandtzaeg et al., 1989). These cells are functionally and phenotypically distinct from peripheral lymphocytes and from lymphocytes below the epithelial basement membrane within the lamina propria of the gut. The IELs are comprised of two sub-populations, one dependent on the thymic microenvironment for differentiation and the other being thymus independent. It appears that the gastrointestinal epithelium can substitute for the thymic epithelial microenvironment and promote self-nonself education and T cell differentiation for the thymus independent subset of IELs (Lefrarn;ois and Puddington, 1995; Klein, 1996; Saito et al., 1998). In this way, the mucosa} intestinal epithelium is considered to be a primary lymphoid organ.
Beneath the basement membrane within the lamina propria is a diversity of immunoinflammatory effector cells of all types including T and B lymphocytes, plasma cells, phagocytes, and dendritic cells, representing a state of “controlled” inflammation primed for host defence (Shanahan, 1994). The existence of this physiologic controlled inflammatory infiltrate is a defining feature of mucosa} tissues. Although the close anatomic juxtaposition of epithelial and immune cells is particularly suited to intercellular communication, each of the cellular components within the mucosa} microenvironment transmits and receives regulatory signals from adjacent cells, and this molecular cross-talk has a conditioning effect on mucosa} structure and function (Shanahan, 1994). Indeed, genetically engineered disruption of any component of the mucosa} microenvironment, including the epithelium, mucosa} T cells, cytokines or the enteric glial cells, as has been achieved with several murine models, is associated with impaired mucosa} defence and uncontrolled inflammation (Shanahan, 1994b; Bush et al., 1998; Shanahan and O’Sullivan, 1999).