title: IL-32 induces indoleamine 2,3-dioxygenase+CD1c+dendritic cells and indoleamine 2,3-dioxygenase+CD163+macrophages: Relevance to mycosis fungoides progression.
abstract: Mycosis fungoides (MF) progresses from patch to tumor stage by expansion of malignant T-cells that fail to be controlled by protective immune mechanisms. In this study, we focused on IL-32, a cytokine, highly expressed in MF lesions. Depending on the other cytokines (IL-4, GM-CSF) present duringin vitroculture of healthy volunteers' monocytes, IL-32 increased the maturation of CD11c+myeloid dendritic cells (mDC) and/or CD163+macrophages, but IL-32 alone showed a clear ability to promote dendritic cell (DC) differentiation from monocytes. DCs matured by IL-32 had the phenotype of skin-resident DCs (CD1c+), but more importantly, also had high expression of indoleamine 2,3-dioxygenase. The presence of DCs with these markers was demonstrated in MF skin lesions. At a molecular level, indoleamine 2,3-dioxygenase messenger RNA (mRNA) levels in MF lesions were higher than those in healthy volunteers, and there was a high correlation between indoleamine 2,3-dioxygenase and IL-32 expression. In contrast, Foxp3 mRNA levels decreased from patch to tumor stage. Increasing expression of IL-10 across MF lesions was highly correlated with IL-32 and indoleamine 2,3-dioxygenase, but not with Foxp3 expression. Thus, IL-32 could contribute to progressive immune dysregulation in MF by directly fostering development of immunosuppressive mDC or macrophages, possibly in association with IL-10.
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University , New York, NY, USA.
authors.forename: Hanako
authors.initials: H
authors.lastname: Ohmatsu
authors.affiliation: Department of Dermatology and Allergy, Skin Cancer Center Charité, Charité- Universitätsmedizin Berlin , Berlin, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Humme
authors.affiliation: Rockefeller University Center for Clinical and Translational Science , New York, NY, USA.
authors.forename: Juana
authors.initials: J
authors.lastname: Gonzalez
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University , New York, NY, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Gulati
authors.affiliation: Department of Dermatology and Allergy, Skin Cancer Center Charité, Charité- Universitätsmedizin Berlin , Berlin, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Möbs
authors.affiliation: Department of Dermatology and Allergy, Skin Cancer Center Charité, Charité- Universitätsmedizin Berlin , Berlin, Germany.
authors.forename: Wolfram
authors.initials: W
authors.lastname: Sterry
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University , New York, NY, USA.
authors.forename: James G
authors.initials: JG
authors.lastname: Krueger
keywords: CD163+ macrophages; CD1c+ dendritic cells; IL-32; indoleamine 2,3-dioxygenase (IDO); mycosis fungoides