Contents lists available at ScienceDirect Cytokine journal homepage: www.elsevier.com/locate/cytokine Inflammatory chemokine profiles and their correlations with effector CD4 T cell and regulatory cell subpopulations in cutaneous lupus erythematosus Silvia Méndez-Flores a , Gabriela Hernández-Molina b, ⁎ , Daniel Azamar-Llamas b , Joaquín Zúñiga c,d , Juanita Romero-Díaz b , Janette Furuzawa-Carballeda b, ⁎ a Department of Dermatology, Instituto Nacional de Ciencias Médicas y Nutrición, Vasco de Quiroga No. 15, Colonia Belisario Domínguez Sección XVI, 14080 Mexico City, Mexico b Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición, Vasco de Quiroga No. 15, Colonia Belisario Domínguez Sección XVI, 14080 Mexico City, Mexico c Laboratory of Immunobiology and Genetics, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico d School of Medicine and Health Sciences, Tecnológico de Monterrey, Mexico City, Mexico ARTICLE INFO Keywords: Chemokines Cutaneous lupus Discoid lupus Subacute cutaneous lupus ABSTRACT We compared the chemokine/receptor expression in skin biopsies of discoid (SLE/DLE) and subacute lupus (SLE/SCLE) and correlated it with tissue and circulating effector CD4 T cells/regulatory cells. Skin biopsies and peripheral blood from 9 active SLE/DLE patients, 9 SLE/SCLE patients, 5 control SLE patients without cutaneous lesions and 10 control healthy donors were included. Clinical skin activity was measured by Cutaneous Lupus Erythematosus Disease Area and Severity Index scoring, and systemic activity was measured by a modified SLEDAI-2K excluding the cutaneous items. Pain and pruritus were evaluated by a 10-point visual analogue scale. To determine the frequencies of CXCL-10/CXCR3-, CCL2/CCR2-, CCL17/CCR4-, CCL20/CCR6-, CCL27/CCR10-, CXCL8/CXCR1-, CXCL13/CXCR5-, IL-22-, CD4/IL-17A-, CD4/IL-4-, CD4/IFN-γ-, CD123/IDO-, CD25/Foxp3-, and CD20/IL-10-expressing cells, double immunostaining procedures were performed. Circulating CD4+/ CD161-/IL-22+, CD4+/CD161+/IL-17+, CD4+/CD25-/IL-4+, CD4+/CD25-/IFN-γ+, CD4+/CD25hi/ Foxp3+, CD3+/CD19+/CD38hi/IL-10+, and CD123+/CD196+/IDO + cells were analyzed by flow cyto- metry. Results: In the tissue, CXCL10, CXCR5, and CCL20 expression and IL-22+, CD4+/IL-17+, CD4+/IFN-γ + and CD123+/IDO + cell percentages were increased in SLE/DLE versus SLE/SCLE. Circulating CD4+/CD161-/IL- 22+, CD4+/CD161+/IL-17+, CD4+/CD25-/IFN-γ+, CD19+/CD38hi/IL-10 + and CD123+/CD196+/ IDO + cell percentages were higher in SLE/DLE versus SLE/SCLE. In the tissue, we found positive correlations between CXCR3 and CD4+/IL-17 + cells; CCR2 and CD4+/IFN-γ + cells; and CCR10 and CD123+/ IDO + cells in the SLE/DLE patients and between CXCL13 and CD20+/IL-10 + cells in the SLE/SCLE patients. In the peripheral blood, we determined positive correlations between CXCR5 and CD4+/CD25-/IFN-γ + cells; CCL17 and CD4+/CD161-/IL-22 + cells; and CCL17 and CD4+/CD161+/IL-17 + cells in the SLE/DLE pa- tients and between CXCR5 and CD3+/CD19+/CD38hi/IL-10 + cells; CCR2 and CD4+/CD25hi/Foxp3 + cells; and CXCR1 and CD4+/CD25hi/Foxp3 + cells in the SLE/SCLE patients. Positive correlations between the pain score and the expression of CCL2 and CCR6 expression were found in the SLE/SCLE patients. In conclusion, the correlations between the expression of chemokines/receptors and subpopulations of ef- fector/regulatory cells showed differential responses among the cutaneous pathologies. 1. Introduction Cutaneous lupus erythematosus (CLE) is an inflammatory disease that encompasses diverse clinical features. Its pathogenesis is complex, multifactorial and still not defined. Although there is a broad spectrum of histological subsets, the overall histological finding in CLE is char- acterized by moderately dense to dense perivascular and peri- appendageal lymphocytic infiltrates in the papillary and reticular dermis with abundant mucin deposition in the reticular dermis [1]. The cell infiltration of the skin may be explained by the presence of https://doi.org/10.1016/j.cyto.2019.03.010 Received 10 November 2018; Received in revised form 8 March 2019; Accepted 14 March 2019 ⁎ Corresponding authors. E-mail addresses: gabyhm@yahoo.com (G. Hernández-Molina), jfuruzawa@gmail.com (J. Furuzawa-Carballeda). Cytokine 119 (2019) 95–112 1043-4666/ © 2019 Published by Elsevier Ltd. T