The Innate and Adaptive Immune System as Targets for Biologic Therapies in Inflammatory Bowel Disease

Abstract

Inflammatory bowel disease (IBD) is an immune-mediated inflammatory condition causing inflammation of gastrointestinal and systemic cells, with an increasing prevalence worldwide. Many factors are known to trigger and maintain inflammation in IBD including the innate and adaptive immune systems, genetics, the gastrointestinal microbiome and several environmental factors. Our knowledge of the involvement of the immune system in the pathophysiology of IBD has advanced rapidly over the last two decades, leading to the development of several immune-targeted treatments with a biological source, known as biologic agents. The initial focus of these agents was directed against the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) leading to dramatic changes in the disease course for a proportion of patients with IBD. However, more recently, it has been shown that a significant proportion of patients do not respond to anti-TNF-α directed therapies, leading a shift to other inflammatory pathways and targets, including those of both the innate and adaptive immune systems, and targets linking both systems including anti-leukocyte trafficking agents-integrins and adhesion molecules. This review briefly describes the molecular basis of immune based gastrointestinal inflammation in IBD, and then describes how several current and future biologic agents work to manipulate these pathways, and their clinical success to date.

Heme protects intestinal mucosal barrier in DSS‐induced colitis through regulating macrophage polarization in both HO‐1‐dependent and HO‐1‐independent way

“…In IBD, the mucosal immune response is initiated by the interaction among activated intestinal epithelium, infiltrated innate myeloid cells, and antigens 33 . By immuno‐histochemistry and immunofluorescence staining with CD11b, F4/80 or CD68 and MPO, we found that large number of monocytes, macrophages and neutrophils were recruited to intestinal lesion site in vehicle mice (Figure 2B,C).…”

Singular manifolds of proteomic drivers to model the evolution of inflammatory bowel disease status

“…Likewise, the role of the binomial composed by the innate and adaptive immune system in IBD therapies involves dozens of feedback loops invoking and sustaining chronic inflammation. However, how the immune system sparks a particular response to repel an IBD threat remains confusing, though it is thought to be immune and non-immune based, with an accepted role of the gut microbiota and non-immune derived cells of the inflammatory cascade including chemokines and inflammasomes (23). In this case, the multifaceted information process limits the repertoire of the immunological machinery.…”

Systems biology in inflammatory bowel diseases: on the way to precision medicine

“…Since then, 3 other anti-TNF agents have been approved for IBD; adalimumab, certolizumab pegol, and golimumab [200]. Beyond anti-TNF agents, many other biological therapies against proinflammatory ILs, such as ustekinumab, intracellular signaling targets, such as Janus kinase inhibitors (tofacitinib, filgotinib, and upadacitinib), and cell adhesion molecules, such as natalizumab, vedolizumab, etrolizumab, AJM300 and PF-00547659 either have been approved for IBD treatment or are currently under investigation in clinical trials [200][201][202][203][204].…”