Interferon-g (IFN-g) is a critical cytokine in formation of multinucleated giant cells (MGCs). Macrophage fusion receptor (MFR) and its ligand CD47 have been implicated in facilitating cell fusion and cell-to-cell recognition in specialized multinucleated giant cells, for example, osteoclasts and foreign body giant cells. There appear to be genetic susceptibility factors for development of sarcoidosis. The involved cytokines in granuloma formation are of the T-helper-1 (Th1) phenotype. Sarcoidosis patients have a high number of T-regulatory cells. Polymorphisms of CARD15/NOD2 have been associated with Crohn's disease. Citrullination, a posttranslation modification process, has been demonstrated to increase peptide and major histocompatibility complex (MHC) affinity, suggesting it can modulate immune responses.
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