New Treatments: Targeting TSLP

In June of 2010, a study was conducted by researchers Zheng, Ma, de Paiva, Cunningham, Hwang, Pflugfelder and Li from the Department of Ophthalmology at Baylor College of Medicine and published in Investigative Ophthalmology & Visual Science. The study focuses on targeting the mediator, thymic stromal lymphopoietin (TSLP), to reduce the inflammatory response associated with an allergic reaction. Before delving into the study, let's take a look at the role of TSLP in an inflammatory response:

- Allergen enters the body and binds to receptors on a type of white blood cell called a B cell

- B cells digest the allergen and present it to a type of white blood cell called a CD4+ TH2 helper cell

- TH2 cells secrete mediators called cytokines IL-4 and IL-5

- IL-4 and IL-5 induce B cells to differentiate into another type of white blood cell called a plasma cell, which then secretes the IgE antibody

- IgE antibodies bind to mast cells

If you remember, the IgE antibodies on the mast cells are ready to bind allergen, activating the mast cell to release histamine and other inflammatory mediators, such as arachadonic acid. In this general scheme of the allergic response, TSLP's role is activation of TH2 cells:

- Allergen stimulates epithelial cells, like the conjunctiva, to release TSLP

- TSLP activates a type of white blood cell called a dendritic cell (DC)

- DCs release mediators that activate TH2 cells, which release IL-4 and IL-5

- IL-4 and IL-5 increase B cell differentiation into plasma cells and release of IgE

- IgE antibodies bind to mast cells

So you can see that TSLP also plays a role in the inflammatory response. The effect of TSLP is comparable to an antigen-bound B cell because both are involved in activating the TH2 cells to release IL-4 and IL-5. With all the different types of white blood cells and the mediators they release, it can get a little confusing.

The take-home message is that the immediate effects of TSLP produce the end-result of IgE antibodies binding to mast cells, which can now bind allergens and produce the inflammatory response. The function of TSLP has been shown in the lungs, gut and skin, but not the eyes...

This study was used to identify the presence of TSLP in allergic conjunctivitis because it hasn't been proven to be involved in the inflammatory process of the eye. An allergic reaction was induced in the experimental group of mice multiple times, using pollen extract. Another group of mice did not receive the pollen extract, serving as the control. After the last allergic reaction, the conjunctiva was harvested from both the experimental and control groups, and the genetic sequences analyzed for expression of the TSLP mediator.

The researchers found a significantly increased expression of TSLP genes in the experimental group compared to the control group. Although the results are promising, much of the study is theoretical and more experiments must be conducted to determine if TSLP really plays a key role in the inflammatory response. If TSLP is determined to play a causative role in the inflammatory response, it serves as a new target for drugs aimed at preventing allergic conjunctivitis.

For information about TSLP Click Here

To view another TSLP study from Clinical & Molecular Allergy Click Here