Monocyte‐derived dendritic cells from C rohn's disease patients exhibit decreased ability to activate T helper type 17 responses in memory cells

Summary An increased activation of interleukin ( IL )‐17 A ‐producing immune cells is a well‐established feature of C rohn's disease ( CD ). Mechanisms that contribute to this aberrant immune activation are, however, less clear. Given that an enhanced induction of innate‐immunity associated cytokines IL ‐6 and IL ‐23, which promote IL ‐17 immunity, is also clearly implicated in CD , we hypothesized that monocyte‐derived dendritic cells (mo DC s) of CD patient origin would mount exaggerated IL ‐17 A responses in T cells. However, we found a significantly attenuated up‐regulation of the IL ‐17 A response in allogeneic T helper memory cells in the presence of culture media from lipopolysaccharide ( LPS )‐stimulated mo DC s of CD patients when compared with mo DC s of control subjects (median fold‐increase in IL ‐17 A m RNA expression 1·09 versus 1·44, P  = 0·038). This was accompanied by a lower expression of IL ‐1β and IL ‐6 transcripts in the LPS ‐treated mo DC s (median 9·55 versus 13·9 relative units, P  = 0·042, and 2·66 versus 9·06 relative units, P  = 0·049, respectively). In addition, the up‐regulation of autophagy‐related LC 3 transcripts was decreased in mo DC s of CD patients (median fold‐increase in m RNA expression 1·22 versus 1·52, P  = 0·029). Our findings reveal similar immunological aberrancies in CD in the general population as reported in CD patients with mutated intracellular bacterial sensor NOD 2, namely attenuated activation of innate cytokines and impaired autophagy, combined with a reduced capacity to up‐regulate the T helper type 17 ( T h17) response. The results presented here emphasize a defective anti‐microbial response in the pathogenesis of CD . The increased mucosal T h1 and T h17 responses, which may contribute to the pathogenesis, could be the consequences of primary defects in the innate immunity.