Appendicitis in children is a leading acute surgical condition in children worldwide. It is commonly caused by infection of the obstructed appendix by enteric gram-negative bacteria. Mucosa-associated invariant T (MAIT) cells are the largest population of antimicrobial T cells in humans and are widely distributed along the gastrointestinal tract (GIT). In a separate study, we showed that MAIT cells activation and recruitment into the appendix drives inflammation and tissue damage in acute appendicitis.
In this study, we found MAIT cell accumulation in the inflamed appendix was linked with infiltration of neutrophils as well as elevated levels of multiple pro-inflammatory chemokines, including CCL17 and CCL22. This was coupled by accumulation of MAIT cells with elevated expression of CCR4 – the chemokine receptor for CCL17 and CCL22. Moreover, we found an enrichment of CCL17- and CCL22-producing CD45+ pan-leukocytes within the inflamed appendix. Further analyses indicate that the predominant leukocyte sources of CCL17 and CCL22 within the appendix were infiltrating neutrophils and B cells. Spearman’s analyses indicated that the levels of MAIT cells within the inflamed appendix were positively correlated with the levels of CCL17+ and CCL22+ infiltrating pan-leukocytes and neutrophils. Interestingly, plasma levels of the inflammatory marker C-reactive protein (CRP) were also positively correlated with the levels of CCL17+ pan-leukocytes and neutrophils within the inflamed appendix.
Taken together, our results suggest that appendix infiltration by CCL17- and CCL22-producing leukocytes, particularly neutrophils and B cells, may drive MAIT cell recruitment during acute appendicitis. Future studies will need to ascertain the significance of CCL17 and CCL22 and their cellular sources as well as the mechanisms underlying production of these chemokines in the pathogenesis of acute appendicitis in children.