P107 IL-34 and IL-36 family expressing cytotoxic T-cells and plasmacytoid dendritic cells are increased in patients with active inflammatory bowel disease
G. Fonseca Camarillo*1, E. Iturriaga Goyon2, J. Furuzawa Carballeda3, J. Yamamoto Furusho2
1Instituto Nacional de Ciencias Médicas y Nutrición, Inflammatory Bowel Disease Clinic, Department of Gastroenterology, Mexico, Mexico, 2Instituto Nacional de Ciencias Médicas y Nutrición, Inflammatory Bowel Disease Clinic. Department of Gastroenterology, Mexico, Mexico, 3Instituto Nacional de Ciencias Médicas y Nutrición, Department of Immunology and Rheumatology, Mexico, Mexico
Inflammatory bowel disease (IBD) is characterised by an imbalance between innate and adaptive immunity leading to the stimulation of T-helper responses with preponderance of pro-inflammatory cytokines. Increase production of proinflammatory cytokines such as the IL-36 family results in inflammation and autoimmune disease. However, IL-34 and IL-36 family intestinal expression and synthesis by cytotoxic T-cells and plasmacytoid dendritic cells in IBD patients have yet to be described.
A cross-sectional comparative study included 45 patients with UC, 24 with Crohn’s disease and 30 normal controls without evidence of intestinal inflammation by endoscopy and histology. Total RNA was extracted from intestinal tissue, and Cdna was obtained by polymerase chain reaction (PCR). Gene expression of IL-34, IL-36 alpha, IL-36 beta, and IL-36 gamma was performed by RT-PCR, and protein expression was detected by immunohistochemistry. The statistical analysis was performed using SPSS version 17.0, using Kruskall–Wallis non-parametric test, Spearman’s correlation, Fisher’s exact test, and odds ratio (OR) to determine the strength of association. A p-value < 0.05 was considered statistically significant.
Interleukin-34, IL-36 alpha, IL-36 beta, and IL-36 gamma mRNAs were detected and quantitated by RT-qPCR in colonic biopsies from UC patients, CD patients and non-inflammatory control tissues. Results showed that IL-34 and IL-36 gamma mRNA expression were increased in colonic mucosa from patients with active UC as compared with CD groups and non-inflammatory control group (p < 0.05). To determine in situ IL-34 and IL-36 family protein expression in intestinal biopsies from active UC and active CD patients, tissues were immunostained and compared with non-inflammatory control tissue. The IL-34 and IL-36 gamma–producing plasmacytoid dendritic cells were increased in active CD versus active UC and non-inflammatory tissues (p < 0.05). Conversely, IL-34 and IL-36 gamma–producing CD8+ T-cells were increased in active UC versus active CD and non-inflammatory tissues (p < 0.05). IL-34–producing cells were found mainly in mucosa, submucosa, adventitia, and perivascular inflammatory infiltrates. The IL-36 gama was expressed largely by epithelial cells, myeloid cells, and fibroblasts, according to morphological identification.
This is the first depiction of the expression and production by cytotoxic T-cells and plasmacytoid dendritic cells IL-34+ and IL-36 gamma+ in IBD. The IL-34 and IL-36 producing plasmacytoid dendritic cells and CD8+ T-cells were increased in active IBD patients compared with non-inflammatory tissues. These cytokines could significantly shape and differentiate inflammatory process and severity between UC and CD pathophysiology.