CD38: biomarker and functional role in human macrophages

Abstract Macrophages mediate innate immune responses via a spectrum of phenotypes that range from inflammatory to resolving. We previously identified CD38 as a robust marker of inflammatory macrophages useful in both murine in vitro and in vivo models. We hypothesized that CD38 plays a similar biomarker and/or functional role in human macrophages and autoimmune inflammatory disease. Using human macrophages of primary or monocytic cell line origin, we found that CD38 is robustly induced in human macrophages exposed to LPS and IFN-g inflammatory stimuli, but not with the alternative stimulus, IL-4. Analyses in the systemic autoimmune disease Systemic Lupus Erythematosus (SLE) revealed that CD38hi classical and non-classical monocyte subpopulations are associated with disease activity. In addition, genetic or pharmacologic CD38 loss-of-function in human primary macrophages resulted in suppressed inflammatory cytokines IL-6 and IL-12p40 secretion in human primary macrophages. Taken together, these findings support a biomarker and functional role for CD38 in inflammatory macrophages/monocytes and inflammatory disease.