Decrease of Skin Infiltrating and Circulating CCR10+ T Cells Coincides with Clinical Improvement after Topical Tacrolimus in Omenn Syndrome  Claudia M. Faaij, Nicola E. Annels, Geertje Ruigrok, Mirjam van der Burg, Lynne M. Ball, Robbert G. Bredius, Maarten J. van Tol, Arjan C. Lankester  Journal of Investigative Dermatology  Volume 130, Issue 1, Pages 308-311 (January 2010) DOI: 10.1038/jid.2009.196 Copyright © 2010 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 1 Decrease of circulating CCR10+ T cells and normalization of skin histology during tacrolimus treatment of a patient with Omenn syndrome (OS1). (a) Flow cytometry shows an increased percentage of circulating CD4+CCR10+ and CD8+CCR10+ T cells. Tacrolimus treatment resulted in a substantial decrease in the number of these T cells. Numbers in the plots represent the percentage of CCR10+ cells within CD4+ or CD8+ T cells. This decrease is also true for the absolute numbers as depicted in (b). The significant cutaneous improvement on topical tacrolimus treatment is depicted in (c). (d) Before treatment, an active lesion with prominent epidermal hyperplasia (H&E stain; scale bar=10μm), a large T-cell infiltrate of both CD4+ (green) and CD8+ T cells (yellow; scale bar=50μm), a reduced epidermal expression of CD1a+ Langerhans cells (red; scale bar=50μm), and a strong expression of CCL27 (single enzymatic staining; scale bar=5μm) are observed. During treatment, normal skin histology was restored with a limited T-cell infiltrate, an increased number of epidermal CD1a+ cells and a basal expression of CCL27 (comparable with healthy control skin, data not shown). Immunohistochemical analysis was performed as described previously (Faaij et al., 2006). The dotted white line represents the epidermal–dermal border. Journal of Investigative Dermatology 2010 130, 308-311DOI: (10.1038/jid.2009.196) Copyright © 2010 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 2 Intracellular cytokine staining reveals a pro-inflammatory profile of the circulating CCR10+ T cells from OS1, which is reduced upon topical tacrolimus treatment. Intracellular staining of cytokines (IFN-γ, TNF-α, IL-2, IL-4, and IL-5) produced by circulating CD4+CCR10+ and CD8+CCR10+ T cells on PMA/ionomycin stimulation in vitro before and during topical tacrolimus treatment. Journal of Investigative Dermatology 2010 130, 308-311DOI: (10.1038/jid.2009.196) Copyright © 2010 The Society for Investigative Dermatology, Inc Terms and Conditions