Abstract
Sarcoidosis is a chronic granulomatous disorder characterized by an accumulation of
lymphocytes and macrophages in the alveoli. Ultimately, long-lasting, nontreated disease
results in a distortion of the microarchitecture of the lower respiratory tract. Our
current understanding of its pathogenesis is that several sequential immunological
events finally resulting in granuloma formation are involved: (1) dependent on a susceptible
genetic background described by a variety of functional polymorphisms (2) the exposure
to one or several still elusive antigen(s), leads to (3) an activation of macrophages,
(4) an attainment of T cell immunity against the antigen(s) mediated by antigen processing
and presentation by macrophages, and finally to (5) induction of granuloma formation.
In this article, a detailed review on cellular and molecular mechanisms underpinning
the sarcoid granulomatous lesion will be given. The important role of alveolar macrophages,
T lymphocytes, regulatory T cells, and various cytokines/chemokines in orchestrating
the induction, evolution, and immunoregulation of the sarcoid granulomatous/fibrotic
lesions will be underscored. Although an etiological agent for sarcoidosis has not
been identified, plausible “sarcoid antigens” including mycobacterial antigens such
as mKatG or ESAT-6, antigens from Propionibacterium acnes, or even self-antigens will be discussed. It is possible that not one single causative
agent exists but several germs, microbial products, or inorganic substances might
induce pathogenetic mechanisms leading to a disease called sarcoidosis.
Keywords
sarcoidosis - granuloma - sarcoid antigens - macrophages - antigen presentation -
T lymphocytes - immunoregulation
