Thymic Stromal Lymphopoietin, or TSLP, is a protein that functions as a signaling molecule, or cytokine, within the body’s immune system. It is often characterized as an “alarm” molecule that alerts the immune system to potential issues. Two main forms exist: a long-form variant that is induced during inflammation and a short-form that is present at a steady level.
The Role of TSLP in the Body
TSLP is primarily produced and released by epithelial cells. These cells form the body’s barrier tissues—the first line of defense—including the skin, the lining of the lungs, and the gastrointestinal tract. The release of TSLP from these locations is a direct response to tissue stress or damage.
Specific triggers can prompt epithelial cells to secrete TSLP. Exposure to allergens like pollen or dust mites, pathogens such as viruses and bacteria, or physical injury can all initiate its release. Once released, TSLP acts as an initial signal, alerting the broader immune system that a potential threat has been detected at one of the body’s defensive surfaces.
TSLP and Allergic Inflammation
TSLP is a primary initiator of Type 2 inflammation, the immune response that underlies most allergic diseases. When external triggers cause an overproduction of TSLP, it sets off an inflammatory cascade by interacting with its specific receptor on various immune cells.
One of the first cells TSLP activates are dendritic cells, which are messengers for the immune system. TSLP instructs these cells to promote the development of T helper 2 (Th2) cells. These Th2 cells are orchestrators of the allergic response, producing signals that recruit other inflammatory cells to the site of irritation.
The cascade continues as TSLP and the activated Th2 cells influence other immune cells. TSLP directly activates mast cells, which release histamine and other substances that cause immediate allergy symptoms. It also promotes the activity of innate lymphoid cells (ILC2s), basophils, and eosinophils, which all contribute to the persistent inflammation seen in chronic allergic conditions.
Medical Conditions Linked to TSLP
The overproduction of TSLP is a factor in several medical conditions involving chronic allergic inflammation. Severe asthma is a prominent example, where elevated TSLP in the airways contributes to inflammation, bronchoconstriction, and mucus production. This TSLP-driven Type 2 inflammation is often resistant to standard treatments like corticosteroids.
Atopic dermatitis, a chronic form of eczema, is also strongly linked to TSLP. In this condition, TSLP is overexpressed in the skin’s keratinocytes, which drives barrier dysfunction, intense itching, and visible inflammation. This can perpetuate a cycle of itching and scratching that further damages the skin and triggers more TSLP release.
Other conditions associated with high TSLP activity include chronic rhinosinusitis with nasal polyps and eosinophilic esophagitis. In the former, TSLP-driven inflammation leads to polyp growth and sinus symptoms. In the latter, it contributes to the buildup of eosinophils in the esophagus, causing swallowing difficulty and tissue damage.
Targeting TSLP for Treatment
Understanding TSLP’s role in allergic inflammation has led to targeted therapies that block its activity. This approach uses biologic medications called monoclonal antibodies, which are laboratory-engineered proteins designed to bind to a specific target like the TSLP protein.
Tezepelumab is a monoclonal antibody created to target TSLP. The antibody circulates through the body and binds to TSLP proteins, preventing them from attaching to their receptors on immune cells. By intercepting the TSLP molecule, the medication stops the inflammatory cascade before it begins, blocking the activation of dendritic cells, Th2 cells, and other players in the allergic response.
This treatment is considered for patients with severe, uncontrolled asthma who do not respond well to other therapies. Targeting an “upstream” trigger like TSLP disrupts the inflammatory process at an early stage. This makes it an effective option for a broad group of individuals with severe asthma, regardless of their specific inflammatory markers.