The dendritic cell: its role in intestinal inflammation and relationship with gut bacteria

Abstract

Dendritic cells are antigen presenting cells that are likely to be pivotal in the balance between tolerance and active immunity to commensal microorganisms that is fundamental to inflammatory conditions, including Crohn's disease and ulcerative colitis. Interactions between dendritic cells and microbial products are discussed and how they contribute to regulation of immune responses. The concept that interactions between dendritic cells and commensal organisms may be responsible for maintaining intestinal immune homeostasis is also explored.

Figure 1

Scanning electron micrograph of a human dendritic cell (from the work of Brigid Balfour, courtesy of Nick English).

Figure 2

The life history of dendritic cells (DC). DC precursors derived from the bone marrow (BM) migrate via peripheral blood to lymphoid tissue or non-lymphoid tissue where they briefly reside as “immature” cells capable of efficient antigen uptake but expressing low levels of costimulatory molecules. In response to cytokines and microbial products, these DC migrate to draining lymph nodes and mature into highly immunostimulatory cells. Some DC constitutively migrate as non-activated or partially activated cells and these DC may play a role in tolerance.

Figure 3

Closely related organisms or microbial products can stimulate dendritic cells (DC) to make different cytokines and as a consequence can shape a developing T cell response. IL, interleukin; LPS, lipopolysaccharide. (See text for details.)

Figure 4

Sampling by dendritic cells (DC) of antigens in the intestinal lumen. At least four pathways have been described by which DC can acquire gut antigens: (1) following transport of antigens by M cells; (2) by reaching between epithelial cells directly into the lumen; (3) via the epithelium, either by uptake of material transported by epithelial cells or following uptake of apoptotic epithelial cells; and (4) by direct access to antigens as a result of breaks in the integrity of the epithelium.

Figure 5

Control of tissue specific lymphocyte homing by dendritic cells (DC). DC draining from the intestine, but not the skin, can induce expression of the mucosal homing integrin α4β7 on naïve T cells that they activate. In conjunction with the possible induction of other molecules associated with homing to the intestine (for example, CCR9) this expression may allow DC to target effector cells efficiently to the site of intestinal antigenic challenge. By analogy, molecules associated with lymphocyte homing to the skin (for example, CLA, P-selectin ligand, CCR4, or CCR10) may be induced by skin draining DC.

Figure 6

The origin of tissue specific dendritic cell functions. Gut dendritic cells (DC) (illustrated in light grey) and non-intestinal DC (dark grey) have tissue specific functions. These might result from the action of local microenvironmental factors on a common precursor (A) or from migration of distinct functionally committed precursors (B) or a combination of both mechanisms. The integrin β7 is expressed by some human DC precursors and may contribute to homing of some DC to the gut. BM, bone marrow.