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IL-23-Polarized Dendritic Cells Drive Responses to Skin Immunization

Oct 19, 2016 5:08:18 PM / by Stacy Matthews Branch, DVM, PhD

TLR4 ligands are released by the keratinocytes upon skin scratching.Atopic dermatitis (AD) is an inflammatory skin disease that affects over 15% of children in the U.S. A common feature of AD is thickening of skin that is dry, irritated, and itchy. There is a disruption in the skin’s function as a barrier to injurious agents. Most cases of AD are allergy related. That is, the skin is sensitized to an offending substance (allergen). This skin immunization or allergic response is worsened by physical scratching action.

Understanding the process involved in these responses in AD can lead to the development of effective treatments. It is known that the cytokine IL-22 causes keratinocytes (outer skin cells) to divide and multiply leading to skin thickening. Another cytokine, IL-23, is produced by dendritic cells, keratinocytes, macrophages, and other cells in the skin. IL-23 produced by dendritic cells acts on T-cells for IL-22 to be produced. What is not fully understood is what causes the dendritic cells to produce IL-23 in response to contact by skin allergens.

To better understand the AD allergic response (and the related responses to scratching), researchers conducted mouse and human skin studies. In mice, the scratching was mimicked by tape stripping (repeated application and removal of adhesive tape) the skin of mice, and then a test allergen was applied. The arms of human volunteers were carefully scratched (superficially without drawing blood). Samples of the mouse and human skin were analyzed at the microscopic level, IL-23 levels were measured, and the dendritic cells were collected and analyzed.

The researchers found that factors normally present within the skin (TLR4 ligands) are released by the keratinocytes upon skin scratching. This in turn causes the keratinocytes to release IL-23. This then causes dendritic cells to also release IL-23. This IL-23 released by the dendritic cells activates T-cells. This results in secretion of IL-22 that responds to the allergen, leading to skin thickening. This information can support the basis of new treatments targeting these processes.

At HemaCare, we offer highly specialized dendritic cells to help researchers further their studies. Order your cells today online or call (877) 397-3087.

Resource:
Yoon, Juhan et al. "IL-23 Induced In Keratinocytes By Endogenous TLR4 Ligands Polarizes Dendritic Cells To Drive IL-22 Responses To Skin Immunization". The Journal of Experimental Medicine 213.10 (2016): 2147-2166. Web. 19 Oct. 2016.

Topics: Dendritic Cells, skin immunization

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