Reduced numbers of mucosal DR^int macrophages and increased numbers of CD103⁺ dendritic cells during anti-TNF-α treatment in patients with Crohn’s disease

Abstract

Objective Anti-TNF-α treatment constitutes a mainstay in the treatment of Crohn’s disease (CD), but its mechanisms of action are not fully understood. We aimed to investigate the effects of adalimumab, a human monoclonal TNF-α antibody, on macrophage (MQ) and dendritic cell (DC) subsets in mucosal biopsies and peripheral blood. Material and methods Intestinal biopsies and blood samples were obtained from 12 different CD patients both before and 4 weeks after the initiation of the induction of adalimumab treatment. Endoscopic disease activity was estimated by the Simple Endoscopic Score for Crohn’s Disease. Biopsies were obtained from inflamed and non-inflamed areas. The numbers of lamina propria CD14 ⁺ DR^int and CD14 ⁺ DR^hi MQs, CD141⁺, CD141⁻ and CD103⁺DCs subsets, and circulating monocytes and DCs were analyzed using flow cytometry. Results At baseline, we observed higher numbers of DR^int MQs and lower numbers of CD103⁺DCs in inflamed versus non-inflamed mucosa [843 vs. 391/10⁵ lamina propria mononuclear cells (LPMCs) (p < 0.05) and 9 vs. 19 × 10⁵ LPMCs (p = 0.01), respectively]. After four weeks of adalimumab treatment, the numbers of DR^int MQs decreased [843 to 379/10⁵ LPMCs (p = 0.03)], whereas the numbers of CD103⁺DCs increased [9–20 × 10⁵ LPMCs (p = 0.003)] compared with baseline. In peripheral blood, no alterations were observed in monocyte or DC numbers between baseline and week 4. Conclusions In CD, mucosal inflammation is associated with high numbers of DR^int MQs and low numbers of CD103⁺DCs. This composition of intestinal myeloid subsets is reversed by anti-TNF-α treatment. These results suggest that DR^int MQs play a pivotal role in CD inflammation.

KEYWORDS:

• Adalimumab
• anti-TNF-α treatment
• Crohn’s disease
• dendritic cell
• macrophage

Disclosure statement

Jørgen Agnholt is a member of the Advisory Board of AbbVie, Denmark. The other authors have no conflicting personal interests to declare.

Funding information

This work was supported by unrestricted grants from AbbVie, Denmark, the foundations of Ruth and Richard Julin, OE and Edla Johansson and Längmanska Kultur and LUA-ALF Clinical Research.