Origin and Function of Monocytes in Inflammatory Bowel Disease

Abstract

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a chronic disease resulting from the interaction of various factors such as social elements, autoimmunity, genetics, and gut microbiota. Alarmingly, recent epidemiological data points to a surging incidence of IBD, underscoring an urgent imperative: to delineate the intricate mechanisms driving its onset. Such insights are paramount, not only for enhancing our comprehension of IBD pathogenesis but also for refining diagnostic and therapeutic paradigms. Monocytes, significant immune cells derived from the bone marrow, serve as precursors to macrophages (Mφs) and dendritic cells (DCs) in the inflammatory response of IBD. Within the IBD milieu, their role is twofold. On the one hand, monocytes are instrumental in precipitating the disease's progression. On the other hand, their differentiated offsprings, namely moMφs and moDCs, are conspicuously mobilized at inflammatory foci, manifesting either pro-inflammatory or anti-inflammatory actions. The phenotypic spectrum of these effector cells, intriguingly, is modulated by variables such as host genetics and the subtleties of the prevailing inflammatory microenvironment. Notwithstanding their significance, a palpable dearth exists in the literature concerning the roles and mechanisms of monocytes in IBD pathogenesis. This review endeavors to bridge this knowledge gap. It offers an exhaustive exploration of monocytes' origin, their developmental trajectory, and their differentiation dynamics during IBD. Furthermore, it delves into the functional ramifications of monocytes and their differentiated progenies throughout IBD's course. Through this lens, we aspire to furnish novel perspectives into IBD's etiology and potential therapeutic strategies.

Keywords: IBD; inflammatory response; monocytes.

Figure 1

Recruitment of Immune Cells by Monocytes in IBD. Through the secretion of cytokines, including chemokines and other inflammatory mediators, monocytes facilitate the congregation of these immune cells. These cells collectively contribute to either the amplification or the regulation of the inflammatory response integral to the pathogenesis of IBD, thereby influencing the disease’s progression and outcomes.

Figure 2

Development and Migration of Monocytes in IBD Pathogenesis. Monocytes originate from hematopoietic stem cells (HSC) in the bone marrow and undergo a sequential process of differentiation, culminating in the formation of monocytes. These monocytes primarily access the circulation through the CCL/CCR2 axis. In the context of IBD, a range of cytokines, chemokines, integrins, adhesion molecules, and gut microenvironmental cues mediate the migration of circulating monocytes to sites of inflammation. Once monocytes infiltrate the gut, they differentiate into macrophages and dendritic cells, ultimately leading to immune response.

Figure 3

Functional heterogeneity and duality of monocytes in IBD. (A) Monocytes exhibit functional heterogeneity, with different subtypes displaying distinct functional characteristics. (B) The stimulation of various cytokine receptors, triggered by the underlying causes of IBD, activates downstream inflammatory signaling pathways, which increasing pro-inflammatory gene expression. This results in heightened inflammation and, through interactions with other immune cells, exacerbates intestinal damage. (C) Monocytes also produce anti-inflammatory cytokines during IBD, fostering immune regulatory interactions that aid in intestinal repair.