Elevations in T-helper-2-initiating cytokines (interleukin-33, interleukin-25 and thymic stromal lymphopoietin) in lesional skin from chronic spontaneous ('idiopathic') urticaria.

Abstract

BACKGROUND:

The mechanism of wealing in chronic spontaneous urticaria (CSU) is largely unknown. We previously demonstrated increased expression of T-helper 2 [interleukin (IL)-4 and IL-5] cytokines in skin biopsies from CSU. This suggested that Th2-initiating cytokines [IL-33, IL-25 and thymic stromal lymphopoietin (TSLP)], released through innate immune mechanisms, may play a role in pathogenesis.

OBJECTIVES:

To identify Th2-initiating cytokines in lesional and nonlesional skin from patients with CSU and to compare the results with a control group.

METHODS:

Paired biopsies (one from a 4-8 h spontaneous weal and one from uninvolved skin) were taken from eight patients with CSU and nine control subjects, and studied by immunohistochemistry and confocal microscopy.

RESULTS:

There were increases in IL-4(+) and IL-5(+) cells in lesional skin vs. controls (P = 0·03 and P < 0·001, respectively) and marked elevations in the numbers of IL-33(+), IL-25(+) and TSLP(+) cells in the dermis of lesional skin vs. both nonlesional skin (P = 0·002, P = 0·01 and P = 0·04, respectively) and controls (P = 0·001, P < 0·001 and P = 0·005, respectively). There was also a correlation between the numbers of IL-33(+) and IL-25(+) cells (r = 0·808, P = 0·015). IL-33 localized to CD31(+) endothelial cells, CD90(+) fibroblasts, CD68(+) macrophages and tryptase(+) mast cells, whereas IL-25 was expressed by epithelial cells, mast cells and major basic protein-positive eosinophils. IL-33 and IL-25 were constitutively expressed in the epidermis of both controls and patients with CSU.

CONCLUSIONS:

Increased expression of Th2-initiating cytokines in lesional skin in CSU suggests that innate pathways might play a role in the mechanism of wealing. As Th2-initiating cytokines play a role in mast cell activation, inflammation and vascular leakage in CSU, these findings may also have therapeutic implications.

• Authors: A B Kay, P Clark, M Maurer, S Ying
• Journal: The British journal of dermatology (Br J Dermatol) Vol. 172 Issue 5 Pg. 1294-302 ( 2015) ISSN: 1365-2133 [Electronic] England
• PMID: 25523947 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 British Association of Dermatologists.

Chemical References

• Cytokines
• Interleukin-17
• Interleukin-33
• Interleukin-5
• Interleukin-4
• Thymic Stromal Lymphopoietin

Topics

• Adult
• Aged
• Case-Control Studies
• Chronic Disease
• Connective Tissue Cells (immunology)
• Cytokines (metabolism)
• Endothelial Cells (immunology)
• Female
• Granulocytes (immunology)
• Humans
• Immunity, Innate (immunology)
• Immunohistochemistry
• Interleukin-17 (metabolism)
• Interleukin-33 (metabolism)
• Interleukin-4 (metabolism)
• Interleukin-5 (metabolism)
• Lymphocytosis (immunology)
• Male
• Microscopy, Confocal
• Middle Aged
• Th2 Cells (immunology)
• Urticaria (immunology)
• Thymic Stromal Lymphopoietin