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 language | English |
|---|---|
| Pages (from-to) | 464-480 |
| Number of pages | 17 |
| Journal | International Journal of Biological Sciences |
| Volume | 15 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 2019 Jan 1 |
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All Science Journal Classification (ASJC) codes
- Ecology, Evolution, Behavior and Systematics
- Applied Microbiology and Biotechnology
- Molecular Biology
- Developmental Biology
- Cell Biology
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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 journal › Article
TY - JOUR
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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U2 - 10.7150/ijbs.25743
DO - 10.7150/ijbs.25743
M3 - Article
C2 - 30745835
AN - SCOPUS:85060891797
VL - 15
SP - 464
EP - 480
JO - International Journal of Biological Sciences
JF - International Journal of Biological Sciences
SN - 1449-2288
IS - 2
ER -