TL1A primed dendritic cells activation exacerbated chronic murine colitis

Tumor necrosis factor-like ligand 1A (TL1A) has been proved to activate adaptive immunity in inflammatory bowel disease (IBD). However, its role in the regulation of intestinal dendritic cells (DCs) has not been fully characterized. This study aims to investigate the modulation of TL1A in DCs activation in murine colitis.

Myeloid TL1A-Transgenic C57BL/6 mice and wild-type (WT) mice were administrated with dextran sulfate sodium (DSS) to explore the effects of TL1A in murine colitis. Bone marrow-derived DCs (BMDCs) were isolated to detect the ability of antigen phagocytosis and presentation. The expression of nuclear factor-κB (NF-κB) pathway and chemokines receptors (CCRs) was assessed by real-time PCR and Western blot.

Myeloid cells with constitutive TL1A expression developed worsened murine colitis with exacerbated T_H1/T_H17 cytokine responses. Intestinal DCs from TL1A transgenic mice expressed high levels of costimulatory molecules (CD80 and CD86) with increased pro-inflammatory cytokines of IL-1β, TNF-α and IL-12/23 p40. Mechanistic studies showed that TL1A enhanced the phagocytotic ability of BMDCs. Moreover, TL1A enhanced the capacity of antigen process and presentation in BMDCs. Besides, TL1A induced the phosphorylation of NF-κB(p65) and IκBα. Meanwhile, higher expression of CCR2, CCR5, CCR7, and CX3CR1 was observed both in vivo and in vitro.

TL1A exacerbated DSS-induced chronic experimental colitis, probably through activation and migration of dendritic cells, and therefore increasing the secretion of pro-inflammatory cytokines.