Inflammatory bowel diseases are associated with dysregulated immune responses in the intestinal tissue. Four molecularly identified macrophage subsets control immune homeostasis in healthy gut. However, the specific roles and transcriptomic profiles of the phenotypically heterogeneous CD14 + macrophage-like population in inflamed gut remain to be investigated in Crohn's disease (CD). Here we identified two phenotypically, morphologically and functionally distinct colonic HLADR + SIRPα + CD14 + subpopulations that were further characterized using single-cell RNA-sequencing (scRNAseq) in CD. Frequencies of CD64 hi CD163 −/dim cells selectively augmented in inflamed colon and correlated with endoscopic score of disease severity. IL-1β and IL-23-producing CD64 hi CD163 −/dim cells predominated over TNF-α-producing CD64 hi CD163 hi cells in lesions. Purified "inflammatory monocyte-like" CD163 − , but not "macrophage-like" CD163 hi cells, through IL-1β, promoted Th17/Th1 but not Th1 responses in tissue memory CD4 + T cells. Unsupervised scRNAseq analysis that captures the entire HLADR + SIRPα + population revealed six clusters, two of which were enriched in either CD163 − or CD163 hi cells, and best defined by TREM1/FCAR/FCN1/IL1RN or CD209/MERTK/MRCI/CD163L1 genes, respectively. Selected newly identified discriminating markers were used beyond CD163 to isolate cells that shared pro-Th17/Th1 function with CD163 − cells. In conclusion, a molecularly distinct pro-inflammatory CD14 + subpopulation accumulates in inflamed colon, drives intestinal inflammatory T-cell responses, and thus, might contribute to CD disease severity.

Background-The relapse rate after steroid induced remission in Crohn's disease is high. Aims-To test whether oral pH modified release budesonide (3 × 1 mg/day) reduces the relapse rate and to identify patient subgroups with an increased risk of relapse. Methods-In a multicentre, randomised, double blind study, 179 patients with steroid induced remission of Crohn's disease received either 3 × 1 mg budesonide (n=84) or placebo (n=95) for one year. The primary study aim was the maintenance of remission of Crohn's disease for one year. Results-Patient characteristics at study entry were similar for both groups. The relapse rate was 67% (56/84) in the budesonide group and 65% (62/95) in the placebo group. The relapse curves in both groups were similar. The mean time to relapse was 93.5 days in the budesonide group and 67.0 days in the placebo group. No prognostic factors allowing prediction of an increased risk for relapse or definition of patient subgroups who derived benefit from low dose budesonide were found. Drug related side eVects were mild and no diVerent between the budesonide and the placebo group. Conclusion-Oral pH modified release budesonide at a dose of 3 × 1 mg/day is not eVective for maintaining steroid induced remission in Crohn's disease. (Gut 1998;42:493-496)

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