Precise identification and functional characterisation of human intestinal macrophages in health and disease

Intestinal macrophages have many critical functions, both in maintaining intestinal immunological homeostasis, and in orchestrating responses to pathogens. Not only do they contribute to regulating intestinal immune responses through production of IL-10 and PGE_2, but they also express TLRs and NLRs to sense bacteria, activate NFκB and secrete cytokines. We have previously shown that murine intestinal macrophages differentiate from monocytes, and that this process is altered under inflammatory conditions. Given their importance in intestinal immunity, precise identification and characterisation of human intestinal macrophages is key to understanding their role in inflammatory bowel disease (IBD).

Our recent deep immunophenotyping of human colonic and small intestinal tissue revealed two macrophage populations, differentiated on CD14 expression, similar to those found in our murine studies. Defined as CD64⁺HLA-DR⁺CD206⁺CD14^hi/lo, both macrophage subsets expressed higher levels of IL-10 and TNFα than either blood monocytes or intestinal dendritic cells. To unravel the roles played by macrophages in IBD we are assessing the abundance, proliferative capacity and functions of both these populations under steady state and inflammatory conditions. By performing this characterisation and functional assessment of human macrophages we hope to elucidate specific roles of macrophages in human IBD, to aid development of future therapeutics.