TL1A Expression in Psoriatic Skin

• Expression of TL1A in psoriatic skin [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  Staining intensity of TL1A by IHC in involved psoriatic skin compared to uninvolved and skin from normal controls
  
  

Psoriasis is a common autoimmune disease; affecting approximately 2 % of the western population. Among these 15% are estimated to have severe disease that requires systemic therapy with e.g. methotrexate, cyclosporine or acitretin that are all drugs associated with high frequencies of side-effects. In contrast to this the recent development of the biologic drugs has provided very efficacious and in general well-tolerated new therapeutics. But even with these newer drugs treatment-failures exist and for this group new treatments are needed TNF-like ligand 1A (TL1A) is a novel member of the TNF family of cytokines. Increasing evidence suggests that in addition to TNF-alfa and IFN-gamma psoriasis is also an IL-23 and IL-17 dependent disease so TH1 and TH17 T cells are suggested to be important in driving the disease. Therefore TL1A, which through binding to DR3 influences TH1 and TH17 T cell differentiation, could be an important cytokine in the early inflammatory process in psoriasis. Recently expression of TL1A in psoriatic skin lesions has been demonstrated but the importance of this remains to be investigated.

TL1A exists in both a membrane bound- and a soluble form and is secreted from antigen presenting cells (APCs) such as monocytes, dendritic cells and macrophages in response to stimulation with immune complexes, bacteria or cytokines (TNF-alfa and IL-1beta). Membrane bound TL1A has also been described in T cells. Recently, a new isoform of soluble TL1A (TL1A(V84-L251)) was discovered with functional differences to TL1A(L72-L251. It's unknown whether this isoform is present in psoriatic skin.

Research on TL1A has focused on autoimmune diseases where immune complexes are formed, e.g. rheumatoid arthritis. However, studies have suggested that early pathogenesis in psoriasis could dependent on formation of large complexes between bacterial DNA and the anti-microbial peptide LL-37 which induce cytokine secretion from APC. Cytokines that could lead to TL1A excretion. Whether TL1A can be secreted in this way is unknown.