Dendritic Cells, Macrophages and Monocytes in Allergic Disease

Antigen-presenting cells (APC) are present throughout mucosal surfaces of the skin, gut and respiratory tract. Dendritic cells (DC), the principal APC, receive and translate environmental signals, which promote maturation and migration to draining lymph nodes where DC can induce clonal expansion of antigen-specific naive T cells. The dendritic cell possesses the unique ability to induce differentiation of T cells, determine the nature of the T cell response and imprint the ability of memory T cells to home to peripheral tissues. The principal mucosal DC subset, myeloid-DC, has been implicated in the generation of Th2 cells, thus provoking inflammation in response to allergen challenge in susceptible individuals. Myeloid-DC, however, display functional plasticity and are also responsive to signals, which can promote a tolerogenic phenotype in DC. Tolerance induction at mucosal surfaces is proposed to depend on the induction and expansion by DC of T cells with regulatory function (Treg). Alveolar macrophages, which derive from a monocyte precursor, express an immunosuppressive phenotype in normal individuals, but display enhanced capacity to secrete inflammatory mediators and present antigen in patients with allergic inflammation, thus amplifying the inflammatory cascade. Antigen-presenting cells, therefore, represent a crucial target for novel methods of immunotherapeutic intervention in chronic allergen-driven inflammatory disease.