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Session: ePoster Monitor 1-Basic and Translational Science

eP647 - Dynamics of Blood Monocyte and Intestinal Inflammation in Patients with Crohn's Disease

Monday, June 3, 2024
1:45 PM – 1:50 PM ET, USA
Location: Baltimore Convention Center, Room 318-320

    ePoster Presenter(s)

  • Naoto Fujimoto

    Stuff
    Gastroenterological surgery
    Osaka university
    Suita, Osaka, Japan

    All of the relevant financial relationships listed below have been mitigated.
    This individual has no financial relationships with ineligible companies.

    • Author(s)

  • Takayuki Ogino, MD, PhD

    Associate professor
    Osaka University
    Osaka University
    Suita, Osaka, Japan

    All of the relevant financial relationships listed below have been mitigated.
    This individual has no financial relationships with ineligible companies.

  • MT

    Mitsunobu Takeda, M.D., Ph.D.

    Assistant professor
    Department of Gastroenterological Surgery, Osaka University
    Suita, Osaka, Japan

    Disclosure information not submitted.

  • AH

    Atsushi Hamabe, M.D.,Ph.D.

    Assistant professor
    Gastroenterological surgery
    Suita, Osaka, Japan

    Disclosure information not submitted.

  • NM

    Norikatsu Miyoshi, FASCRS

    Assistant Professor
    Osaka University
    Suita, Osaka, Japan

    Disclosure information not submitted.

  • HY

    Hirofumi Yamamoto, M.D., Ph.D.

    Adjunct professor
    Gastroenterological surgery
    Suita, Osaka, Japan

    Disclosure information not submitted.

  • MU

    Mamoru Uemura, MD, PhD

    Associate Professor
    Osaka University
    Suita City, Osaka, Japan

    Disclosure information not submitted.

  • TM

    Tsunekazu Mizushima, M.D., Ph.D.

    Specially-appointed professor
    Thetapeutics for inflammatory bowel disease
    Suita, Osaka, Japan

    Disclosure information not submitted.

    • Senior Author(s)

  • HE

    Hidetoshi Eguchi, MD, PhD

    Professor
    Graduate School of Medicine, Osaka University
    Suita, Osaka, Japan

    Disclosure information not submitted.

    • Author(s)

  • YD

    Yuichiro Doki, M.D., Ph.D.

    Professor
    Gastroenterological surgery
    Suita, Osaka, Japan

    Disclosure information not submitted.

Purpose/Background: In Crohn's disease (CD), macrophages play a crucial role in the pathogenesis of intestinal inflammation by producing proinflammatory cytokines. Intestinal macrophages were reported as originated from blood monocytes in animal models and induced the migration into the gut through a CCR2-dependent manner. This mechanism could be similar in humans. Monocytosis, characterized by an increase in blood monocyte levels, has been reported in autoimmune diseases, suggesting a link between local inflammation and blood monocytes. In this study, we investigated the association between dynamics of blood monocytes and intestinal inflammation in CD.Methods/Interventions: This study included 206 CD patients who had treatments in Osaka University Hospital between 2011 and 2021. The association between monocytosis and clinicopathological factors were assessed. We also performed cell surface antigen analysis of peripheral blood mononuclear cells (PBMC) using Mass Cytometry, and genomic analysis of lamina propria mononuclear cells (LPMC) and mesenteric lymph nodes (mLN) using microarray and single-cell RNA sequencing. The samples were isolated from CD patients in active (CDAI≥150) and remission phase (CDAI < 150). Monocytosis was defined as monocyte counts exceeding the upper limit of the laboratory's normal range at any point during the study period.Results/Outcomes: Monocytosis was observed in 116 patients (56.3%). The monocytosis group was significantly younger (P=0.049), earlier disease onset (P=0.003), and had higher rates of unscheduled hospital visits (P=0.006). The rates of surgery were also high tendency but not significant (P=0.071). Mass Cytometry showed that CCR4+CXCR3+ monocytes were significantly increased in CD patients compared to healthy controls and HLA-DR- monocytes were significantly increased in active phase. Next, to validate the intestinal migration of blood monocytes, the analysis of LPMC was performed. LPMC were categorized into four populations based on their surface antigens: CD14+CD163low, CD14+CD163high, CD14-CD11c high, and CD14-CD11c- cells. Microarray analysis revealed that CD14+CD163low cells exhibited similarities to blood monocytes with high expression of S100A8/9, IRF5, and SIRPA. Furthermore, to investigate the distribution and gene expression in mLN, single-cell RNA sequencing was performed using mLN samples from CD patients who underwent surgery. In macrophages of mLN, gene expression of S100A8/9, IRF5, SIRPA and CCR7 were high along with increased numbers.Conclusion/

Discussion: In CD patients, blood monocytes differentiated into macrophages and supplied them to the intestine and mLN on active phase.