Evidence for local dendritic cell activation in pulmonary sarcoidosis

We analyzed myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) in broncho-alveolar lavage (BAL) and blood from newly diagnosed, untreated pulmonary sarcoidosis patients and healthy controls using 9-color flowcytometry. DCs, isolated from BAL using flowcytometric sorting (mDCs) or cultured from monocytes (mo-DCs), were functionally assessed in a mixed leukocyte reaction with na？ve allogeneic CD4+ T cells. Using Immunohistochemistry, location and activation status of CD11c+DCs was assessed in mucosal airway biopsies.mDCs in BAL, but not in blood, from sarcoidosis patients were increased in number when compared with mDCs from healthy controls. mDCs purified from BAL of sarcoidosis patients induced T cell proliferation and differentiation and did not show diminished immune reactivity. Mo-DCs from patients induced increased TNFα release in co-cultures with na？ve allogeneic CD4+ T cells. Finally, immunohistochemical analyses revealed increased numbers of mature CD86+ DCs in granuloma-containing airway mucosal biopsies from sarcoidosis patients.Taken together, these finding implicate increased local DC activation in granuloma formation or maintenance in pulmonary sarcoidosis.Sarcoidosis is a systemic disease characterized by the presence of noncaseating granulomas in involved organs, affecting the lung in more than 90% of patients [1,2]. The granulomatous reaction occurs in the absence of a clearly defined immunological target. However, a reaction to an unidentified antigen is suspected [3]. An antigen-driven pathogenesis is supported by disease-associated polymorphisms in genes encoding antigen recognizing or antigen presenting molecules such as Toll-like receptors and MHC class II [4]. Epidemiological and experimental data are suggestive of airborne or infectious antigens, in particular mycobacterial peptides, but attempts to link sarcoidosis to a causative pathogen are difficult and remain controversial [5-7]. Increased numbers of CD4+ T cells in the broncho-alveolar lavage