| dc.description.abstract | Behçet’s disease is a chronic vasculitis with multisystemic involvement. It is characterised by recurrent episodes of inflammation which clinically present as oro- genital and mucocutaneous lesions and, in more severe cases, uveitis and neurological involvements. Monocytes are reported to play a significant role in driving inflammation in BD. While monocytes incite inflammation, much more importantly, they actively stop the process of acute inflammation by resolution. In BD, very little is known about how monocytes resolve inflammation. This study hypothesised that monocytes in BD do not effectively propagate resolution in BD. The hypothesis was confirmed, and the following results were obtained. There was an increased expression of CCL2 and CCR5 genes from monocytes of BD patients. This result suggests that monocytes are sources of inflammatory mediators that propagate inflammation in BD. A reduced expression of chemokine receptors CCR2 and CX3CR1 was reported on the protein level. Proven the functional relevance of CCR2 and CX3CR1 in migration during monocyte inflammatory and resolution phases, respectively, the chemotactic and phagocytic abilities of microbes and apoptotic cells by monocytes of BD patients were investigated. An aberrant migration of monocytes in the BD patients was reported, where the chemotactic migration was comparable to the chemokinetic migration towards recombinant CCL2. Also, a reduced ability of classical monocytes in BD to phagocytose apoptotic cells (Efferocytosis) was reported. Efferocytosis is a crucial driver of resolution and, together with the reduced expression of CX3CR1, suggests that monocytes in BD are defective at initiating resolution. Also, while monocytes from BD patients were observed to be sources of pro-inflammatory chemokines, functionally, the phagocytoses of microbes, which is an inflammatory response, were comparable to HC individuals. Collectively, this study suggests that monocytes may contribute to the pathogenesis of BD primarily by their failure to propagate the resolution of inflammation rather than inciting it. Therefore, this study provides a new insight into approaching inflammation in BD by harnessing the resolution mechanism. New treatment modalities targeting resolution pathways could offer novel approaches to controlling inflammation in BD, especially in patients whose diseases are refractory. | en_US |
