IL-13-stimulated human keratinocytes preferentially attract CD4+CCR4+ T cells: possible role in atopic dermatitis.
Skin inflammation in atopic dermatitis (AD) is characterized by the predominant infiltration of T-helper (Th)2-cells in lesional skin. However, the mechanism of recruitment of these cells in lesional skin of AD is not yet fully elucidated. In this study, we investigated the role of IL-13-stimulated human primary keratinocytes (HPKs) in the recruitment of lymphocytes and further delineated the mechanism of enrichment of these cells. In the migration assays, we observed preferential enrichment of CD4(+)CCR4(+) T cells towards IL-13-stimulated HPKs. Interestingly, CD4(+)CCR4(+) T cells from AD showed a higher chemotactic response than those from healthy individuals. We observed a significant increase in the expression of CCL22 in IL-13-stimulated HPKs as compared to unstimulated cells. Blocking of CCL22 in IL-13-stimulated HPKs by a neutralizing antibody resulted in 70-90% inhibition in migration of CD4(+)CCR4(+) T cells. Moreover, IL-13 upregulated IFN-gamma-induced chemokines, CCL2 and CCL5, in HPKs. Taken together, our data suggest that IL-13-stimulated HPKs participate in a positive feedback loop by preferentially enriching Th2-cells in lesional skin of acute AD patients. However, in chronic phase, IL-13 may act in synergy with IFN-gamma resulting in lymphocytes recruitment of a mixed phenotype at the site of inflammation, thus contributing to the chronification of eczema.
Department of Dermatology and Allergology, Hannover Medical School, Hannover, Germany. purwarrahul@yahoo.com
Rahul
R
Purwar
Thomas
T
Werfel
Miriam
M
Wittmann
D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D002465:Cell Movement; D002478:Cells, Cultured; D054422:Chemokine CCL22; D019742:Chemokines, CC / Q000096:biosynthesis; D003876:Dermatitis, Atopic / Q000209:etiology* / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D018793:Interleukin-13 / Q000494:pharmacology*; D015603:Keratinocytes / Q000187:drug effects / Q000502:physiology*; D054398:Receptors, CCR4; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000032:analysis / Q000502:physiology*
C515482:CCL22 protein, human; C515354:CCR4 protein, human; C515187:CXCR3 protein, human; D054422:Chemokine CCL22; D019742:Chemokines, CC; D018793:Interleukin-13; D054398:Receptors, CCR4; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D007371:Interferon-gamma