IL-32 induces indoleamine 2, 3-dioxygenase+CD1c+ dendritic cells and indoleamine 2, 3-dioxygenase+CD163+ macrophages: Relevance to mycosis fungoides progression. (1st February 2017)

• Record Type: Journal Article
• Authors: Ohmatsu, Hanako; Humme, Daniel; Gonzalez, Juana; Gulati, Nicholas; Möbs, Markus; Sterry, Wolfram; Krueger, James G.
• Is Part Of: Oncoimmunology. Volume 6:Number 2(2017)
• Publication Date: 2017-02-01
• Subjects: CD1c+ dendritic cells -- CD163+ macrophages -- IL-32 -- indoleamine 2, 3-dioxygenase (IDO) -- mycosis fungoides; Tumors -- Immunological aspects -- Periodicals; Neoplasms -- therapy -- Periodicals; Immunotherapy -- Periodicals; 616.994
• DOI: 10.1080/2162402X.2016.1181237
• Languages: English
• ISSNs: 2162-402X

Abstract

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 during in vitro culture 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.