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.

Immunosuppressive therapy is frequently used to treat gastrointestinal diseases such as inflammatory bowel disease, autoimmune hepatitis, IgG4-related disease (autoimmune pancreatitis and sclerosing cholangitis) and in the post-transplantation setting. These drugs interfere with the immune system. The main safety concern with their use is the risk of infections. Certain infections can be prevented or their impact minimized. Physicians must adopt preventative strategies and should have a high degree of suspicion to recognize infections early and treat appropriately. This article reviews the risk factors for infections, the mechanism of action of immunosuppressive therapy and proposes preventive strategies.

Background and Aims CD14+ mononuclear phagocytes [MNPs] and T cells infiltrate colon in ulcerative colitis [UC]. Here we investigated how CD14+ MNPs and the cytokines they produce shape the colonic effector T cell profile. Methods Colonic or mesenteric lymph node [mLNs] CD4+ T cells isolated from UC or Crohn’s disease [CD] patients were stimulated with cytokines or autologous CD14+ MNPs. Cytokine expression was assessed by intracytoplasmic staining and multiplex ELISA. Unsupervised phenotypic multicolour analysis of colonic CD14+ MNPs was performed using the FlowSOM algorithm. Results Among CD14+CD64+HLA-DR+SIRPα + MNPs, only the pro-inflammatory cytokine-producing CD163− subpopulation accumulated in inflamed UC colon and promoted mucosal IL-1β-dependent Th17, Th17/Th1, Th17/Th22 but not Th1 responses. Unsupervised phenotypic analysis of CD14+CD64+ MNPs segregated CD163− monocyte-like cells and CD163+ macrophages. Unexpectedly, IL-12, IL-1β and CD163−, but not CD163+, cells induced IL-8 expression in colonic CD4+ T cells, which co-expressed IFN-γ and/or IL-17 in UC and not CD. The CD163− monocyte-like cells increased the frequency of IL-8+IL-17+/−IFN-γ +/− T cells through IL-1β and IL-12. Finally, colonic IL-8+ T cells co-expressing GM-CSF, TNF-α and IL-6 were detected ex vivo and, promoted by IL-12 in the mucosa and mLNs in UC only. Conclusions Our findings established a link between monocyte-like CD163− MNPs, IL-12, IL-1β and the detection of colonic memory IL-8-producing CD4+ T cells, which might all contribute to the pathogenesis of UC.

Summary Neutrophils are detected in inflamed colon in Crohn’s disease (CD). However, whether the frequency and/or activation of circulating or gut tissue neutrophils correlate with endoscopic severity remains to be investigated. A cohort of 73 CD patients was prospectively enrolled according to endoscopic severity and treatment history. Individuals with active disease were stratified using the Montreal classification. Harvey–Bradshaw Index (HBI) and Simple Endoscopic Score for Crohn’s Disease (SES‐CD) were performed at the time of ileocolonoscopy. Frequency of neutrophils and their expression of CD66b and CD64 were assessed in paired blood and colonic biopsies using flow cytometry. The percentage of neutrophils increased in inflamed colon and correlated with SES‐CD in the entire cohort of patients examined, as well as in the subgroup with inflammatory (B1) active disease. SES‐CD further correlated with neutrophil CD66b expression in mucosa but not blood and, conversely, with neutrophil CD64 expression in blood but not mucosa. However, the evaluation of neutrophil activation in mucosa when compared to blood reflected disease activity more clearly. Finally, a neutrophil activation power index (CD66b in mucosa X CD64 in blood) that correlated with SES‐CD discriminated between patients with mild and severe disease. In conclusion, the frequency and activation of colonic neutrophils correlated with SES‐CD, highlighting that mucosal neutrophils are associated with disease severity in CD.

Only half of patients with IBD are aware of the risks of smoking associated with their disease, whereas their intent to quit smoking is directly related to their awareness. In the scope of IBD's treatment, management of smoking cessation should be undertaken in all smokers.