Human DC3 Antigen Presenting Dendritic Cells From Induced Pluripotent Stem Cells

Taiki Satoh; Marcelo A S Toledo; Janik Boehnke; Kathrin Olschok; Niclas Flosdorf; Katrin Götz; Caroline Küstermann; Stephanie Sontag; Kristin Seré; Steffen Koschmieder; Tim H Brümmendorf; Nicolas Chatain; Yoh-Ichi Tagawa; Martin Zenke

doi:10.3389/fcell.2021.667304

Human DC3 Antigen Presenting Dendritic Cells From Induced Pluripotent Stem Cells

Front Cell Dev Biol. 2021 Jul 22:9:667304. doi: 10.3389/fcell.2021.667304. eCollection 2021.

Authors

Taiki Satoh^{1

2

3}, Marcelo A S Toledo^{1

2

4}, Janik Boehnke^{1

2}, Kathrin Olschok⁴, Niclas Flosdorf^{1

2}, Katrin Götz^{1

2}, Caroline Küstermann^{1

2}, Stephanie Sontag^{1

2}, Kristin Seré^{1

2}, Steffen Koschmieder⁴, Tim H Brümmendorf⁴, Nicolas Chatain⁴, Yoh-Ichi Tagawa³, Martin Zenke^{1

2}

Affiliations

¹ Department of Cell Biology, Institute for Biomedical Engineering, RWTH Aachen University Medical School, Aachen, Germany.
² Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, Aachen, Germany.
³ School of Life Sciences and Technology, Tokyo Institute of Technology, Kanagawa, Japan.
⁴ Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University Medical School, Aachen, Germany.

Abstract

Dendritic cells (DC) are professional antigen-presenting cells that develop from hematopoietic stem cells. Different DC subsets exist based on ontogeny, location and function, including the recently identified proinflammatory DC3 subset. DC3 have the prominent activity to polarize CD8⁺ T cells into CD8⁺ CD103⁺ tissue resident T cells. Here we describe human DC3 differentiated from induced pluripotent stem cells (iPS cells). iPS cell-derived DC3 have the gene expression and surface marker make-up of blood DC3 and polarize CD8⁺ T cells into CD8⁺ CD103⁺ tissue-resident memory T cells in vitro. To test the impact of malignant JAK2 V617F mutation on DC3, we differentiated patient-specific iPS cells with JAK2 V617F^het and JAK2 V617F^hom mutations into JAK2 V617F^het and JAK2 V617F^hom DC3. The JAK2 V617F mutation enhanced DC3 production and caused a bias toward erythrocytes and megakaryocytes. The patient-specific iPS cell-derived DC3 are expected to allow studying DC3 in human diseases and developing novel therapeutics.

Keywords: DC3; JAK2; JAK2 V617F; dendritic cells; hematopoiesis; iPS cells; induced pluripotent stem cell.