Secretion, blood levels and cutaneous expression of TL1A in psoriasis patients

Abstract

TL1A is a TNF-like cytokine which has been shown to co-stimulate TH1 and TH17 responses during chronic inflammation. The expression of this novel cytokine has been investigated in inflammatory disorders like rheumatoid arthritis and inflammatory bowel disease, but little is known about expression and induction in psoriasis. Indeed, the pathogenesis in psoriasis is still not fully understood and it is speculated that cytokines other than TNF-α are important in subsets of patients. Also, for patients with severe disease that are treated with systemic anti-TNF-α blockade, novel candidates to be used as disease and response biomarkers are of high interest. Here, we demonstrate TL1A expression in biopsies from psoriatic lesions. Also, we investigated spontaneous and induced TL1A secretion from PBMCs and blood levels from a cohort of psoriasis patients. Here, increased spontaneous secretion from PBMCs was observed as compared to healthy controls and a small subset of patients had highly elevated TL1A in the blood. Interestingly, activation of PBMCs with various cytokines showed a decreased sensitivity for TL1A activation in psoriasis patients compared to healthy controls.TL1A levels in blood and biopsies could not be correlated with disease activity with this patient cohort. Thus, additional large-scale studies are warranted to investigate TL1A as a biomarker.

The Role of Co-Signaling Molecules in Psoriasis and Their Implications for Targeted Treatment

“…Previous studies have shown that both protein expressions and mRNA transcripts of TL1A and DR3 were increased in psoriatic lesions (Bamias et al, 2011). Serum TL1A levels were significantly elevated in patients with psoriasis but not in patients with atopic dermatitis and health control, and the high serum TL1A levels were decreased after treatment (Li et al, 2014;Pedersen et al, 2015). Li et al detected the expression of DR3 in PBMCs of patients with psoriasis and found that there was a positive correlation between the percentage of DR3 + CD8 + and DR3 + CD14 + cells and the PASI scores in patients with psoriasis .…”

Role of TL1A in Inflammatory Autoimmune Diseases: A Comprehensive Review

“…Macrophages overexpressing TL1A promoted secretion of TNF-α and IL-1β ( 26 ). Monocytes secreted TL1A in response to stimulation by immune complexes, leading to enhanced T cell responses ( 5 , 27 ). In inflammatory bowel disease, TL1A is produced in the intestinal lamina propria of macrophages in patients with Crohn’s disease ( 23 ).…”

“…Psoriasis is a common inflammatory skin disease characterized by thickened, scaly, red skin patches ( 73 ). TL1A is predominantly expressed in psoriatic lesions, particularly in infiltrating inflammatory cells, keratinocytes and vascular cells ( 27 , 74 ). TL1A promotes production of IL-17, which induces granulocyte colony-stimulating factor (G-CSF) and chemokine ligand 20 (CCL20) and recruits large number of neutrophils to damaged joints, leading to early inflammation.…”

Multifaceted death receptor 3 signaling—promoting survival and triggering death

“…DR3 and TL1A expression is found in skin lesions, but not in healthy skin areas of patients with active psoriasis, indicating a pathogenic role. Immunohistochemistry and gene expression analysis of psoriatic skin lesions suggest TL1A expression by numerous immune and nonimmune cells, for example, keratinocytes, endothelial cells, neutrophils, lymphocytes, and monocytes .…”