Table 1.

Potential Molecular Targets for Biologic Therapies in Patients with Inflammatory Bowel Disease

Dysregulated molecular mechanism(s) in IBD	Potential molecular target(s)
A. Intestinal epithelial barrier dysfunction
Apoptosis	Apoptotic molecules (e.g., caspase-8)
Translocation of antigens/microbes	Toll-like receptors (e.g., TLR-4)
Antigen-presenting cells	Macrophages, dendritic cells
Paneth cells	Defensins
B. Acute inflammation
Failure of regulatory cells	Regulatory T cells
Activation of proinflammatory mediators	T effector cells (Th1, Th2, Th17) B cells Dendritic cells Macrophages (TGFβ, TNF-α, IFN-γ, cytokines [IL-6, IL-9, IL-12, IL-23])
Signaling pathways	Smad7 JAK inhibitors (e.g., tofacitinib)
Trafficking pathways	Adhesion molecules (e.g., MAdCAM-1) Anti-integrins (e.g., anti-α4β7)
C. Perpetuation of chronic inflammation
Innate intestinal immunity mechanisms	Genes involved in innate mucosal defense and antigen presentation (NOD2, MDR1, PPAR-γ)
Adaptive intestinal immunity mechanisms	Regulatory T cells T effector cells (Th) B cells
Oxidative stress balance	Redox-sensitive signaling pathways and proinflammatory transcription molecules
D. Mucosal healing, tissue destruction	Dendritic cells, adipocytesM Fibroblasts, myofibroblasts

IBD, inflammatory bowel disease; Th, T helper; TGFβ, transforming growth factor β; TNF-α, tumor necrosis factor α; IFN, interferon; IL, interleukin; JAK, Janus-activated kinase; MAdCAM-1, mucosal addressin cellular adhesion molecule-1.