CCR6 Is a Predicting Biomarker of Radiosensitivity and Potential Target of Radiosensitization in Rectal Cancer

Hui Chang,Jia-wang Wei,Ya-lan Tao,Pei-rong Ding,Yun-fei Xia,Yuan-hong Gao,Wei-wei Xiao 대한암학회 2018 Cancer Research and Treatment Vol.50 No.4

Purpose This study aimed to explore the functions and mechanisms of C-C motif chemokine receptor 6 (CCR6), a gene associated with progression and metastasis of colorectal cancer (CRC), in radiosensitivity of rectal cancer (RC). Materials and Methods RNA sequencing and immunohistochemical analysis on CCR6 expression were performed in pretreatment tissues of RC patients exhibiting different therapeutic effects of radiotherapy. Colonogenic survival assay was conducted in different CRC cell lines to assess their radiosensitivity. And the impact of CCR6 expression on radiosensitivity was validated through RNA interference. The DNA damage repair (DDR) abilities of cell lines with different CCR6 expression were evaluated through immunofluorescence-based H2AX quantification. Results The CCR6 mRNA level was higher in patients without pathologic complete remission (pCR) than in those with pCR (fold changed, 2.11; p=0.004). High-level expression of CCR6 protein was more common in the bad responders than in the good responders (76.3% vs. 37.5%, p < 0.001). The CRC cell lines with higher CCR6 expression (LoVo and sw480) appeared to be more radioresistant, compared with the sw620 cell line which had lower CCR6 expression. CCR6 knockdown made the LoVo cells more sensitive to ionizing radiation (sensitization enhancement ratio, 1.738; p < 0.001), and decreased their DDR efficiency. Conclusion CCR6 might affect the RC radiosensitivity through DDR process. These findings supported CCR6 as a predicting biomarker of radiosensitivity and a potential target of radiosensitization for RC patients.

Endoribonucleolytic Cleavage of m⁶A-Containing RNAs by RNase P/MRP Complex

Park, Ok Hyun,Ha, Hongseok,Lee, Yujin,Boo, Sung Ho,Kwon, Do Hoon,Song, Hyun Kyu,Kim, Yoon Ki Elsevier 2019 Molecular cell Vol.74 No.3

<P><B>Summary</B></P> <P> <I>N</I> <SUP>6</SUP>-methyladenosine (m<SUP>6</SUP>A) is the most abundant internal modification in RNAs and plays regulatory roles in a variety of biological and physiological processes. Despite its important roles, the molecular mechanism underlying m<SUP>6</SUP>A-mediated gene regulation is poorly understood. Here, we show that m<SUP>6</SUP>A-containing RNAs are subject to endoribonucleolytic cleavage via YTHDF2 (m<SUP>6</SUP>A reader protein), HRSP12 (adaptor protein), and RNase P/MRP (endoribonucleases). We demonstrate that HRSP12 functions as an adaptor to bridge YTHDF2 and RNase P/MRP, eliciting rapid degradation of YTHDF2-bound RNAs. Transcriptome-wide analyses show that m<SUP>6</SUP>A RNAs that are preferentially targeted for endoribonucleolytic cleavage have an HRSP12-binding site and a RNase P/MRP-directed cleavage site upstream and downstream of the YTHDF2-binding site, respectively. We also find that a subset of m<SUP>6</SUP>A-containing circular RNAs associates with YTHDF2 in an HRSP12-dependent manner and is selectively downregulated by RNase P/MRP. Thus, our data expand the known functions of RNase P/MRP to endoribonucleolytic cleavage of m<SUP>6</SUP>A RNAs.</P> <P><B>Highlights</B></P> <P> <UL> <LI> m<SUP>6</SUP>A-containing RNAs are degraded by an endoribonucleolytic cleavage pathway </LI> <LI> A YTHDF2-HRSP12-RNase P/MRP axis contributes to m<SUP>6</SUP>A-mediated RNA decay </LI> <LI> An interaction between YTHDF2 and RNase P/MRP is bridged by HRSP12 </LI> <LI> m<SUP>6</SUP>A-containing circular RNAs are degraded by the YTHDF2-HRSP12-RNase P/MRP pathway </LI> </UL> </P> <P><B>Graphical Abstract</B></P> <P>[DISPLAY OMISSION]</P>

Psoriasis contain newly identified CCL20-producing Th1/Th17/Th22 cells and CCR6-expressing DC-LAMP+ mature dendritic cells: a possible role of CCL20/CCR6 chemokine system in T cells-mature DCs interaction in chronic psoriasis

( Hyunjoong Jee1 ),( Tae Gyun Kim ),( Wen Hao Wu ),( Dashlkhumbe Byamba ),( James G. Krueger ),( Min Geol Lee ) 대한피부과학회 2011 초록집 Vol.49 No.20

Therapeutic Effects of Erythroid Differentiation Regulator 1 on Imiquimod-Induced Psoriasis-Like Skin Inflammation

Kim, Kyung Eun,Houh, Younkyung,Park, Hyun Jeong,Cho, Daeho MDPI 2016 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.17 No.2

<P>Psoriasis is a common skin disease accompanied by chronic inflammation. In previous studies, erythroid differentiation regulator 1 (ERDR1) was shown to have a negative correlation with proinflammatory cytokine IL-18. However, the role of ERDR1 in the inflammatory skin disease psoriasis has not been evaluated. In this study, to investigate the role of ERDR1 in psoriasis, recombinant ERDR1 was injected intraperitoneally into a psoriasis mouse model. Recombinant ERDR1 (rERDR1) significantly alleviated the symptoms of psoriasis-like skin inflammation and reduced the mRNA of various psoriasis-related markers, including keratin 14, S100A8, and Th17-related cytokines IL-17 and IL-22, suggesting that rERDR1 exerts therapeutic effects on psoriasis via the regulation of Th17 functions. Additionally, the expression of CCL20, a well-known Th17 attracting chemokine, was determined. CCL20 expression significantly decreased in the rERDR1-injected group compared with the vehicle (PBS)-injected group. CCR6 expression in the psoriatic lesional skin was also decreased by rERDR1 administration, implying the inhibition of CCR6-expressing Th17 cell chemotaxis via the downregulation of CCL20. Taken together, this study provides the first evidence that ERDR1 may be a potential therapeutic target for psoriasis.</P>

e-Poster : Statins as possible therapeutic drugs in psoriasis through inhibiting CCL20/CCR6 interaction (초)

김태균,다시카,오문호,제정환,박진모,노효진,백진옥,이민걸 대한피부과학회 2010 초록집 Vol.48 No.20

LIGHT-HVEM Signaling in Innate Lymphoid Cell Subsets Protects Against Enteric Bacterial Infection

Seo, Goo-Young,Shui, Jr-Wen,Takahashi, Daisuke,Song, Christina,Wang, Qingyang,Kim, Kenneth,Mikulski, Zbigniew,Chandra, Shilpi,Giles, Daniel A.,Zahner, Sonja,Kim, Pyeung-Hyeun,Cheroutre, Hilde,Colonna, Elsevier 2018 Cell host & microbe Vol.24 No.2

<P><B>Summary</B></P> <P>Innate lymphoid cells (ILCs) are important regulators of early infection at mucosal barriers. ILCs are divided into three groups based on expression profiles, and are activated by cytokines and neuropeptides. Yet, it remains unknown if ILCs integrate other signals in providing protection. We show that signaling through herpes virus entry mediator (HVEM), a member of the tumor necrosis factor (TNF) receptor superfamily, in ILC3 is important for host defense against oral infection with the bacterial pathogen <I>Yersinia enterocolitica.</I> HVEM stimulates protective interferon-γ (IFN-γ) secretion from ILCs, and mice with HVEM-deficient ILC3 exhibit reduced IFN-γ production, higher bacterial burdens and increased mortality. In addition, IFN-γ production is critical as adoptive transfer of wild-type but not IFN-γ-deficient ILC3 can restore protection to mice lacking ILCs. We identify the TNF superfamily member, LIGHT, as the ligand inducing HVEM signals in ILCs. Thus HVEM signaling mediated by LIGHT plays a critical role in regulating ILC3-derived IFN-γ production for protection following infection.</P> <P><B>Video Abstract</B></P> <P>Display Omitted</P> <P><B>Highlights</B></P> <P> <UL> <LI> ILC3 are required for early host defense during <I>Y. enterocolitica</I> infection </LI> <LI> IFN-γ from CCR6<SUP>−</SUP> ILC3 is essential for protection of mice from <I>Yersinia</I> </LI> <LI> HVEM expression by ILC3 is important for IFN-γ production following infection </LI> <LI> LIGHT is the ligand for HVEM signaling in regulating ILC3-derived IFN-γ production </LI> </UL> </P> <P><B>Graphical Abstract</B></P> <P>[DISPLAY OMISSION]</P>

TNFα and IL-1β in the synovial fluid facilitate mucosal-associated invariant T (MAIT) cell migration

Kim, Miok,Yoo, Su-Jin,Kang, Seong Wook,Kwon, Jaeyul,Choi, Inpyo,Lee, Chang Hoon Elsevier 2017 Cytokine Vol.99 No.-

<P><B>Abstract</B></P> <P>Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that primarily affect the joints and inflammatory cell migration into inflamed articular sites contribute to this disease. Among the inflammatory cells, human mucosal-associated invariant T (MAIT) cells were recently recognized as critical cellular component with a pathological role in RA. However, their migratory characteristics are poorly understood. The aim of this study was to determine whether human MAIT cells preferentially traffick to inflamed synovial sites in rheumatoid arthritis patients and to elucidate the underlying mechanism. First, we found that TNFα and IL-1β were elevated in synovial fluid (SF) of RA patients, which resulted in increased expression of E-selectin, ICAM-1 and V-CAM-1 on blood vessel endothelial cells. To understand whether TNFα and IL-1β in the SF facilitated MAIT cell migration, we analyzed CD161<SUP>+</SUP> TCRα7.2<SUP>+</SUP> MAIT and other CD3<SUP>+</SUP> T cells for differences in migratory capacity. Collectively, our results demonstrate that TNFα and IL-1β in the SF facilitated MAIT cell migration dependent on expression of selectin ligand, sialyl Lewis<SUP>X</SUP> (sLe<SUP>X</SUP>) and CCR6 on MAIT cells. We also showed that MAIT cells in the SF from RA patients equipped upregulated sLe<SUP>X</SUP> compared to the peripheral blood of RA patients and healthy persons, which suggest that TNFα and IL-1β mediated expression of E-selectin preferentially attract sLe<SUP>X</SUP> mediated MAIT cell migration into the SF of RA patients.</P>