Increased Expression of RANTES, CCR3 and CCR5 in the Lesional Skin of Patients with Atopic Eczema

Abstract

Background: Atopic eczema (AE) is a relapsing inflammatory disease based on IgE sensitization and characterized by peripheral blood eosinophilia and eosinophil infiltration into the lesional skin. In the patch test reaction of AE by allergens, an increased infiltration of activated eosinophils has been demonstrated peaking at 24–48 h. Regulated on activation normal T cell expressed and secreted (RANTES/CCL5) is a chemokine that induces eosinophil migration, and CCR3 and CCR5 are the receptors of RANTES. Objective: In order to further clarify the pathomechanisms of eosinophil infiltration in ongoing chronic inflammation in the skin of patients with AE and its relation to disease severity, we examined the expression of RANTES and its receptors CCR3 and CCR5 in challenged and unchallenged lesional skin of AE. Methods: We examined the number of RANTES+ cells, CCR3+ cells, CCR5+cells, activated (EG2+) eosinophils and CD3+ T cells in normal skin of healthy volunteers, and in challenged lesional skin (24 h after mite patch test) as well as unchallenged lesional skin of AE patients by immunohistochemistry. The cellular source of RANTES, CCR3 and CCR5 was analyzed by double immunohistochemistry using specific antibodies to RANTES, CCR3 or CCR5, and antibodies to ECP (EG2) or CD3. Results: The numbers of RANTES+ cells, CCR3+ cells, CCR5+ cells, EG2+ cells and CD3+ cells were all significantly increased in challenged (mite patch-tested) lesional skin of AE patients as compared to those in unchallenged lesional skin and normal skin. The numbers of these cells in unchallenged lesional skin were greater than those in normal skin. The number of EG2+ cells in the unchallenged lesional skin correlated with both the peripheral blood eosinophil count and the SCORAD index. The number of EG2+ cells in challenged lesional skin correlated with the number of CCR5+ cells. Activated eosinophils and T cells expressed RANTES and various proportions of these cells were CCR3+ and CCR5+ in both challenged and unchallenged lesional skin. Conclusion: Taken together, these results suggest that RANTES as well as its receptors CCR3 and CCR5 may play important roles in the orchestration of eosinophil infiltration in ongoing chronic inflammation in AE, and also reflect the severity of disease.

Major differences in inflammatory dendritic cells and their products distinguish atopic dermatitis from psoriasis

“…22,23 We found a substantially higher gene expression of CCL5/RANTES in AD in comparison with psoriasis and normal skin, which probably plays a major role in the orchestration and recruitment of eosinophils in ongoing inflammation in AD. [24][25][26] Our evaluation of DC subsets provides important new information that could help explain T-cell polarization in AD versus psoriasis.…”

Effects of venom immunotherapy on serum level of CCL5/RANTES in patients withHymenopteravenom allergy

“…A growing body of evidence suggests that many cell types present in asthmatic airways, allergic rhinitis and atopic dermatitis have the capacity to generate CCL5/RANTES, which directly supported the potential role of CCL5/RANTES in these diseases 7,9,10,11,16 . Increased expression of CCL5/RANTES was observed in the lesional skin of patients with atopic eczema, and cDNA for CCL5 was upregulated in allergic rhinitis 16,17 . It was also demonstrated that the level of CCL5/RANTES in exhaled breath condensate was significantly correlated with parameters of airflow limitation 18 .…”

Mechanisms of leukocyte trafficking in allergic diseases: insights into new therapies targeting chemokines and chemokine receptors

“…In addition, the axes of chemokines and their receptors for T-cell trafficking are heterogeneous both within disease phenotypes and within patients in allergic diseases. [40] CCL2 MCP-1/MCAF/TDCF AA (BALF), AD (serum, PBMC) [70,89] CCL3 MIP-1α/LD78α AA (BALF), AD (PBMC) [70] CCL3CL1 LD78β CCL4 MIP-1β AD (serum, PBMC) [89] CCL5 RANTES AA (BALF), AD (skin biopsies, serum, PBMC) [70,79,88,89] CCL6 -CCL7 MCP-3 AA (BALF) [79] CCL8 MCP-2 CCL9 -CCL10 -…”

“…In addition, the level of CCL11 in the lavage is significantly correlated with disease activity of allergic rhinitis [87]. In skin lesions of AD patients, CCL5, -11, -13 and -24 upregulation is associated with eosinophil accumulation [88][89][90]. Dermal fibroblasts, mononuclear cells and eosinophils are major sources of these chemokines [88][89][90].…”

“…In skin lesions of AD patients, CCL5, -11, -13 and -24 upregulation is associated with eosinophil accumulation [88][89][90]. Dermal fibroblasts, mononuclear cells and eosinophils are major sources of these chemokines [88][89][90]. The serum levels of CCL11 and CCL26, but not CCL24, are significantly correlated with disease activity in AD [91][92][93].…”