Thymic stromal lymphopoietin

TSLP or thymic stromal lymphopoietin has been described as a "proallergic" IL-7-like cytokine in atopic dermatitis and allergic asthma. It has now been shown that it is also produced in keratinocytes of psoriasis patients (also in keratinocytes of patients with atopic dermatitis), but not in keratinocytes of normal individuals.

Elevated levels of thymic stromal lymphopoietin have been detected in epidermolysis bullosa simplex and are thought to be partly responsible for the itching present in this group of patients. TSLP appears to play a key role in the generation of allergic and non-allergic inflammatory reactions of the skin and mucous membranes. Consequently, this cytokine could be a new target for a promising therapeutic option in psoriasis vulgaris.

Tezepelumab is a human monoclonal antibody of the type IgG2λ (immunoglobulin G2λ), which is produced in Chinese hamster ovary cells (CHO cells) using recombinant DNA technology. It has a molar mass of around 148 kDa. ^{Tezepelumab®} inter venes very early in the inflammatory cascade. The monoclonal antibody neutralizes TSLP (thymic stromal lymphopoietin), which is formed in skin and mucosal epithelia.

TSLP (see also thymic stromal lymphopoietin) has been described as a "proallergic" IL-7-like cytokine in atopic eczema and allergic asthma. It also plays a role in itching in the epidermolysis bullosa simplex group. TSLP activates IL-23 and TNF-alpha production by dendritic cells. It has an activating effect on effector cells such as eosinophil and basophil leukocytes as well as on mast cells and induces the release of T-cell-attracting cytokines in monocytes via the JAK/STAT and MAP kinase signaling pathway. Furthermore, TSLP enhances the maturation process of myeloid dendritic cells (CD11c+).

TSLP transgenic mice develop mixed cryoglobulinemia and membrane proliferative glomerulonephritis.

The connection to SPINK7, a protease inhibitor, is remarkable. Epithelial silencing of SPINK7 promotes the production of proinflammatory cytokines, including thymic stromal lymphopoietin (TSLP).

1. Bromley SK et al (2013) IL-23 induces atopic dermatitis-like inflammation instead of psoriasis-like inflammation in CCR2-deficient mice. doi: 10.1371/journal.pone.0058196.
2. Cianferoni A et al (2014) The importance of TSLP in allergic disease and its role as a potential therapeutic target. Expert Rev Clin Immunol 10:1463-1474
3. Gauvreau GM et al (2014) Effects of an anti-TSLP antibody on allergen-induced asthmatic responses. N Engl J Med 370:2102-2110
4. Hui CC et al (2014) T cell-mediated induction of thymic stromal lymphopoietin in differentiated human primary bronchial epithelial cells. Clin Exp Allergy 44:953-964
5. Kumar V et al (2016) Keratin-dependent thymic stromal lymphopoietin expression suggests a link betweenskin
   blistering and atopic disease. J Allergy Clin Immunol 138:1461-1464.
6. Volpe E et al (2014) Thymic stromal lymphopoietin left keratinocytes and dendritic cell-derived IL-23 in patients with psoriasis. J Allergy Clin Immunol 134:373-381
7. Yadava K et al (2014) Thymic stromal lymphopoietin plays divergent roles in murine models of atopic and nonatopic airway inflammation. Allergy 69:1333-1342