IL-15 generates IFN-γ-producing cells reciprocally expressing lymphoid-myeloid markers during dendritic cell differentiation

Kee Woong Kwon, So Jeong Kim, Hongmin Kim, Woo Sik Kim, Soon Myung Kang, Eunsol Choi, Sang-Jun Ha, Joo Heon Yoon, SungJae Shin

Research output: Contribution to journalArticle

Abstract

Recently, interest in IL-15-differentiated cells has increased; however, the phenotypic definition of IL-15-differentiated bone marrow-derived cells (IL-15-DBMCs) is still under debate, particularly the generation of IFN-γ-producing innate cells such as premature NK (pre-mNK) cells, natural killer dendritic cells (NKDCs), interferon-producing killer dendritic cells (IKDCs), and type 1 innate lymphoid cells (ILC1s), all of which are IL-15-dependent. Here, we revisited the immunophenotypic characteristics of IFN-γ-producing IL-15-DBMCs and their functional role in the control of intracellular Mycobacterium tuberculosis (Mtb) infection. When comparing the cytokine levels between bone marrow-derived dendritic cells (BMDCs) and IL-15-DBMCs upon stimulation with various TLR agonists, only the CD11c int population of IL-15-DBMCs produced significant levels of IFN-γ, decreased levels of MHC-II, and increased levels of B220. Neither BMDCs nor IL-15-DBMCs were found to express DX5 or NK1.1, which are representative markers for the NK cell lineage and IKDCs. When the CD11c int B220 + population of IL-15-DBMCs was enriched, the Thy1.2 + Sca-1 + population showed a marked increase in IFN-γ production. In addition, while depletion of the B220 + and Thy1.2 + populations of IL-15-DBMCs, but not the CD19 + population, inhibited IFN-γ production, enrichment of these cell populations increased IFN-γ. Ultimately, co-culture of sorted IFN-γ-producing B220 + Thy1.2 + IL-15-DBMCs with Mtb-infected macrophages resulted in control of the intracellular growth of Mtb via the IFN-γ-nitric oxide axis in a donor cell number-dependent manner. Taken together, the results indicate that IFN-γ-producing IL-15-DBMCs could be redefined as CD11c int B220 + Thy1.2 + Sca-1 + cells, which phenotypically resemble both IKDCs and ILC1s, and may have therapeutic potential for controlling infectious intracellular bacteria such as Mtb.

Original languageEnglish
Pages (from-to)464-480
Number of pages17
JournalInternational Journal of Biological Sciences
Volume15
Issue number2
DOIs
Publication statusPublished - 2019 Jan 1

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Interleukin-15
dendritic cells
cell differentiation
Dendritic Cells
Cell Differentiation
bone
Bone Marrow Cells
bone marrow
tuberculosis
Mycobacterium tuberculosis
cells
Natural Killer Cells
Interferons
Population
natural killer cells
interferons
marker
Bone Marrow
Mycobacterium Infections
functional role

All Science Journal Classification (ASJC) codes

  • Ecology, Evolution, Behavior and Systematics
  • Applied Microbiology and Biotechnology
  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Cite this

Kwon, Kee Woong ; Kim, So Jeong ; Kim, Hongmin ; Kim, Woo Sik ; Kang, Soon Myung ; Choi, Eunsol ; Ha, Sang-Jun ; Yoon, Joo Heon ; Shin, SungJae. / IL-15 generates IFN-γ-producing cells reciprocally expressing lymphoid-myeloid markers during dendritic cell differentiation. In: International Journal of Biological Sciences. 2019 ; Vol. 15, No. 2. pp. 464-480.
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IL-15 generates IFN-γ-producing cells reciprocally expressing lymphoid-myeloid markers during dendritic cell differentiation. / Kwon, Kee Woong; Kim, So Jeong; Kim, Hongmin; Kim, Woo Sik; Kang, Soon Myung; Choi, Eunsol; Ha, Sang-Jun; Yoon, Joo Heon; Shin, SungJae.

In: International Journal of Biological Sciences, Vol. 15, No. 2, 01.01.2019, p. 464-480.

Research output: Contribution to journalArticle

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T1 - IL-15 generates IFN-γ-producing cells reciprocally expressing lymphoid-myeloid markers during dendritic cell differentiation

AU - Kwon, Kee Woong

AU - Kim, So Jeong

AU - Kim, Hongmin

AU - Kim, Woo Sik

AU - Kang, Soon Myung

AU - Choi, Eunsol

AU - Ha, Sang-Jun

AU - Yoon, Joo Heon

AU - Shin, SungJae

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Recently, interest in IL-15-differentiated cells has increased; however, the phenotypic definition of IL-15-differentiated bone marrow-derived cells (IL-15-DBMCs) is still under debate, particularly the generation of IFN-γ-producing innate cells such as premature NK (pre-mNK) cells, natural killer dendritic cells (NKDCs), interferon-producing killer dendritic cells (IKDCs), and type 1 innate lymphoid cells (ILC1s), all of which are IL-15-dependent. Here, we revisited the immunophenotypic characteristics of IFN-γ-producing IL-15-DBMCs and their functional role in the control of intracellular Mycobacterium tuberculosis (Mtb) infection. When comparing the cytokine levels between bone marrow-derived dendritic cells (BMDCs) and IL-15-DBMCs upon stimulation with various TLR agonists, only the CD11c int population of IL-15-DBMCs produced significant levels of IFN-γ, decreased levels of MHC-II, and increased levels of B220. Neither BMDCs nor IL-15-DBMCs were found to express DX5 or NK1.1, which are representative markers for the NK cell lineage and IKDCs. When the CD11c int B220 + population of IL-15-DBMCs was enriched, the Thy1.2 + Sca-1 + population showed a marked increase in IFN-γ production. In addition, while depletion of the B220 + and Thy1.2 + populations of IL-15-DBMCs, but not the CD19 + population, inhibited IFN-γ production, enrichment of these cell populations increased IFN-γ. Ultimately, co-culture of sorted IFN-γ-producing B220 + Thy1.2 + IL-15-DBMCs with Mtb-infected macrophages resulted in control of the intracellular growth of Mtb via the IFN-γ-nitric oxide axis in a donor cell number-dependent manner. Taken together, the results indicate that IFN-γ-producing IL-15-DBMCs could be redefined as CD11c int B220 + Thy1.2 + Sca-1 + cells, which phenotypically resemble both IKDCs and ILC1s, and may have therapeutic potential for controlling infectious intracellular bacteria such as Mtb.

AB - Recently, interest in IL-15-differentiated cells has increased; however, the phenotypic definition of IL-15-differentiated bone marrow-derived cells (IL-15-DBMCs) is still under debate, particularly the generation of IFN-γ-producing innate cells such as premature NK (pre-mNK) cells, natural killer dendritic cells (NKDCs), interferon-producing killer dendritic cells (IKDCs), and type 1 innate lymphoid cells (ILC1s), all of which are IL-15-dependent. Here, we revisited the immunophenotypic characteristics of IFN-γ-producing IL-15-DBMCs and their functional role in the control of intracellular Mycobacterium tuberculosis (Mtb) infection. When comparing the cytokine levels between bone marrow-derived dendritic cells (BMDCs) and IL-15-DBMCs upon stimulation with various TLR agonists, only the CD11c int population of IL-15-DBMCs produced significant levels of IFN-γ, decreased levels of MHC-II, and increased levels of B220. Neither BMDCs nor IL-15-DBMCs were found to express DX5 or NK1.1, which are representative markers for the NK cell lineage and IKDCs. When the CD11c int B220 + population of IL-15-DBMCs was enriched, the Thy1.2 + Sca-1 + population showed a marked increase in IFN-γ production. In addition, while depletion of the B220 + and Thy1.2 + populations of IL-15-DBMCs, but not the CD19 + population, inhibited IFN-γ production, enrichment of these cell populations increased IFN-γ. Ultimately, co-culture of sorted IFN-γ-producing B220 + Thy1.2 + IL-15-DBMCs with Mtb-infected macrophages resulted in control of the intracellular growth of Mtb via the IFN-γ-nitric oxide axis in a donor cell number-dependent manner. Taken together, the results indicate that IFN-γ-producing IL-15-DBMCs could be redefined as CD11c int B220 + Thy1.2 + Sca-1 + cells, which phenotypically resemble both IKDCs and ILC1s, and may have therapeutic potential for controlling infectious intracellular bacteria such as Mtb.

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