Publications by authors named "Zhong-Yin Li"

5 Publications

  • Page 1 of 1

The transcriptional repressor ID2 supports natural killer cell maturation by controlling TCF1 amplitude.

J Exp Med 2021 Jun;218(6)

Department of Pathology, Committees on Immunology and Cancer Biology, The University of Chicago, Chicago, IL.

Gaining a mechanistic understanding of the expansion and maturation program of natural killer (NK) cells will provide opportunities for harnessing their inflammation-inducing and oncolytic capacity for therapeutic purposes. Here, we demonstrated that ID2, a transcriptional regulatory protein constitutively expressed in NK cells, supports NK cell effector maturation by controlling the amplitude and temporal dynamics of the transcription factor TCF1. TCF1 promotes immature NK cell expansion and restrains differentiation. The increased TCF1 expression in ID2-deficient NK cells arrests their maturation and alters cell surface receptor expression. Moreover, TCF1 limits NK cell functions, such as cytokine-induced IFN-γ production and the ability to clear metastatic melanoma in ID2-deficient NK cells. Our data demonstrate that ID2 sets a threshold for TCF1 during NK cell development, thus controlling the balance of immature and terminally differentiated cells that support future NK cell responses.
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http://dx.doi.org/10.1084/jem.20202032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056751PMC
June 2021

Transcription factor ID2 prevents E proteins from enforcing a naïve T lymphocyte gene program during NK cell development.

Sci Immunol 2018 04;3(22)

Department of Pathology and Committee on Immunology, University of Chicago, Chicago, IL 60657, USA.

All innate lymphoid cells (ILCs) require the small helix-loop-helix transcription factor ID2, but the functions of ID2 are not well understood in these cells. We show that mature natural killer (NK) cells, the prototypic ILCs, developed in mice lacking ID2 but remained as precursor CD27CD11b cells that failed to differentiate into CD27CD11b cytotoxic effectors. We show that ID2 limited chromatin accessibility at E protein binding sites near naïve T lymphocyte-associated genes including multiple chemokine receptors, cytokine receptors, and signaling molecules and altered the NK cell response to inflammatory cytokines. In the absence of ID2, CD27CD11b NK cells expressed ID3, a helix-loop-helix protein associated with naïve T cells, and they transitioned from a CD8 memory precursor-like to a naïve-like chromatin accessibility state. We demonstrate that ID3 was required for the development of ID2-deficient NK cells, indicating that completely unfettered E protein function is incompatible with NK cell development. These data solidify the roles of ID2 and ID3 as mediators of effector and naïve gene programs, respectively, and revealed a critical role for ID2 in promoting a chromatin state and transcriptional program in CD27CD11b NK cells that supports cytotoxic effector differentiation and cytokine responses.
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http://dx.doi.org/10.1126/sciimmunol.aao2139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6750718PMC
April 2018

Cytochrome P450 26A1 modulates natural killer cells in mouse early pregnancy.

J Cell Mol Med 2017 04 17;21(4):697-710. Epub 2016 Nov 17.

State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.

Cytochrome P450 26A1 (CYP26A1) has a spatiotemporal expression pattern in the uterus, with a significant increase in mRNA and protein levels during peri-implantation. Inhibiting the function or expression of CYP26A1 can cause pregnancy failure, suggesting an important regulatory role of CYP26A1 in the maintenance of pregnancy. However, little is known about the exact mechanism involved. In this study, using a pCR3.1-cyp26a1 plasmid immunization mouse model and a Cyp26a1-MO (Cyp26a1-specific antisense oligos) knockdown mouse model, we report that the number of Dolichos biflorus agglutinin (DBA) lectin-positive uterine natural killer (uNK) cells was reduced in pCR3.1-cyp26a1 plasmid immunized and Cyp26a1-MO-treated mice. In contrast, the percentage of CD3 CD49b NK cells in the uteri from the treatment group was significantly higher than that of the control group in both models. Similarly, significantly up-regulated expression of CD49b (a pan-NK cell marker), interferon gamma, CCL2, CCR2 (CCL2 receptor) and CCL3 were detected in the uteri of pCR3.1-cyp26a1- and Cyp26a1-MO-treated mice. Transcriptome analysis suggested that CYP26A1 might regulate NK cells through chemokines. In conclusion, the present data suggest that silencing CYP26A1 expression/function can decrease the number of uNK cells and significantly increase the percentage of CD3 CD49b NK cells in the uteri of pregnant mice. These findings provide a new line of evidence correlating the deleterious effects of blocking CYP26A1 in pregnancy with the aberrant regulation of NK cells in the uterus.
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http://dx.doi.org/10.1111/jcmm.13013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5345621PMC
April 2017

Seminal plasma induces inflammation in the uterus through the γδ T/IL-17 pathway.

Sci Rep 2016 04 25;6:25118. Epub 2016 Apr 25.

State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, P.R. China.

After insemination, a large number of leukocytes migrate into the uterus, which is accompanied by intense inflammation. However, the details of how seminal plasma interacts with the uterus are still not very clear. Here, we present that neutrophils migrate and accumulate around the uterine epithelium following insemination, which is accompanied by an increase in interleukin (IL) 17A levels. Additionally, we find that γδ T cells are the major source of IL-17A, and the seminal plasma could induce the γδ T cells to secret IL-17A. Blocking IL-17A could reduce the number of neutrophils in the uterus and prevent them from migrating to the epithelium by decreasing the chemokines CXCL1, CXCL2 and CXCL5. Blocking IL-17A did not affect the Th1/Th2 balance but actually diminished the inflammation in the uterus by reducing the expression of IL-1β and TNF-α. In summary, we found a new mechanism by which seminal plasma could influence the inflammation in the uterus through the γδ T/IL-17 pathway to regulate the expression of various chemokines and cytokines.
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http://dx.doi.org/10.1038/srep25118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4842971PMC
April 2016

IFN-γ modulates Ly-49 receptors on NK cells in IFN-γ-induced pregnancy failure.

Sci Rep 2015 Dec 11;5:18159. Epub 2015 Dec 11.

State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, P.R. China.

We have previously shown that interferon gamma (IFN-γ) induces aberrant CD49b(+) natural killer (NK) cell recruitment by regulating CX3CL1 and eventually provokes foetal loss. In this study, we show that IFN-γ also modulates Ly-49 receptors on NK cells during pregnancy failure. The percentages of Ly-49A(+) and Ly-49G2(+) NK cells in the uteri of the IFN-γ-treated group were significantly lower than those observed in the control group. Moreover, the median fluorescence intensity (MFI) values of Ly-49A and Ly-49G2 expression on NK cells in the uteri of the IFN-γ-treated group were significantly lower than those of the control group. Using isolated spleen leucocytes, we further found that IFN-γ significantly reduced the percentage of Ly-49A(+) NK cells in vitro. However, CX3CL1 was not involved in the modulation of Ly-49 receptors, and the expression of CX3CR1 was not regulated by IFN-γ in spleen leucocytes. Collectively, our data indicate that IFN-γ can modulate Ly-49 receptors on NK cells and this process may play a role in IFN-γ-induced pregnancy failure. Thus, we provide a new line of evidence correlating the deleterious effects of IFN-γ with its role in regulating NK cell Ly-49 receptors during pregnancy failure.
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http://dx.doi.org/10.1038/srep18159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4676035PMC
December 2015