Effects of Thermotherapy on Th1/Th2 Cells in Esophageal Cancer Patients Treated with Radiotherapy

Hong, Mei,Jiang, Zao,Zhou, Ying-Feng Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.5

Background: To investigate the effects of double radiofrequency hyperthermia on Th1/Th2 cells in esophageal cancer patients treated with radiotherapy. Materials and Methods: 22 patients with esophageal cancer were divided into a radiotherapy group (10 cases) and a combined group (double radiofrequency hyperthermia combined with radiotherapy group, 12 cases). Both groups received conventional radiotherapy using a cobalt-60 therapy apparatus (TD60-66Gy/30-33F). Patients in the combined group also underwent double radiofrequency hyperthermia (2F/W, 8-10F). Before and after treatment, Th1, Th2, Tc1 and Tc2 cells in peripheral blood were determined with flow cytometry. Results: In the radiotherapy group, Th1 cell contents before and after radiotherapy were $17.5{\pm}5.26%$ and $9.69{\pm}4.86%$, respectively, with a significant difference (p<0.01). The Th1/Th2 ratio was significantly decreased from $28.2{\pm}14.3$ to $16.5{\pm}10.4 $(p<0.01). In the combined group, Th1 cell content before radiotherapy was $15.9{\pm}8.18%$, and it increased to $18.6{\pm}8.84$ after radiotherapy (p>0.05), the Th1/Th2 ratio decreasing from $38.4{\pm}36.3$ to $28.1{\pm}24.0$ (p>0.05). Changes in Th2, Tc1 and Tc2 cell levels were not significant in the two groups before and after therapy (p>0.05). Conclusions: Double radiofrequency hyperthermia can promote the conversion from Th2 to Th1 cells, and regulate the balance of Th1/Th2 cells.

MiR-1165-3p Suppresses Th2 Differentiation via Targeting IL-13 and PPM1A in a Mouse Model of Allergic Airway Inflammation

Zhengxia Wang,Ningfei Ji,Zhongqi Chen,Zhixiao Sun,Chaojie Wu,Wenqing Yu,Fan Hu,Mao Huang,Mingshun Zhang 대한천식알레르기학회 2020 Allergy, Asthma & Immunology Research Vol.12 No.5

Purpose: CD4+T cells are essential in the pathogenesis of allergic asthma. We have previously demonstrated that microRNA-1165-3p (miR-1165-3p) was significantly reduced in T-helper type (Th) 2 cells and that miR-1165-3p was a surrogate marker for atopic asthma. Little is known about the mechanisms of miR-1165-3p in the regulation of Th2-dominated allergic inflammation. We aimed to investigate the associations between Th2 differentiation and miR-1165b-3p in asthma as well as the possible mechanisms. Methods: CD4+ naïve T cells were differentiated into Th1 or Th2 cells in vitro. MiR-1165-3p was up-regulated or down-regulated using lentiviral systems during Th1/Th2 differentiation. In vivo, the lentiviral particles with the miR-1165-3p enhancer were administered by tail vein injection on the first day of a house dust mite -induced allergic airway inflammation model. Allergic inflammation and Th1/Th2 differentiation were routinely monitored. To investigate the potential targets of miR-1165-3p, biotin-microRNA pull-down products were sequenced, and the candidates were further verified with a dual-luciferase reporter assay. The roles of a target protein phosphatase, Mg2+/Mn2+-dependent 1A (PPM1A), in Th2 cell differentiation and allergic asthma were further explored. Plasma PPM1A was determined by ELISA in 18 subjects with asthma and 20 controls. Results: The lentivirus encoding miR-1165-3p suppressed Th2-cell differentiation in vitro. In contrast, miR-1165-3p silencing promoted Th2-cell development. In the HDM-induced model of allergic airway inflammation, miR-1165-3p up-regulation was accompanied by reduced airway hyper-responsiveness, serum immunoglobulin E, airway inflammation and Th2-cell polarization. IL-13 and PPM1A were the direct targets of miR-1165-3p. The expression of IL-13 or PPM1A was inversely correlated with that of miR-1165-3p. PPM1A regulated the signal transducer and activator of transcription and AKT signaling pathways during Th2 differentiation. Moreover, plasma PPM1A was significantly increased in asthmatic patients. Conclusions: MiR-1165-3p negatively may regulate Th2-cell differentiation by targeting IL-13 and PPM1A in allergic airway inflammation.

정상 성인 말초혈액 내 CD4+ 및 CD8+ 림프구 아군의 구성 비율

한윤수 충북대학교 의과대학 충북대학교 의학연구소 1998 忠北醫大學術誌 Vol.8 No.1

연구목적 : 본 연구에서는 정상 성인의 말초혈액에서 분리한 CD4+ 및 CD8+ 림프구 각각에서 T helper 1(Th1)과 T helper 2(Th2) 림프구 및 T cytotoxic 1(Tc1)과 T cytotoxic 2(Tc2) 림프구의 구성비율을 알아보고, 이것으로부터 Th1/Th2 비와 Tc1/Tc2 비를 계산하고자 하였다. 대상 및 방법 : 이와 같은 목적을 위해 분리한 말초혈액 단핵세포를 CD4 또는 CD8에 대한 염색을 실시한 후 세포내 IFN-γ와 IL-4에 대한 염색을 실시하였으며, 결과는 유세포 분석을 이용해 관찰하였다. 본 연구에서는 20명의 건강한 성인 남녀를 대상으로 하였으며, 이들의 연령은 22.36 ±3.54 세였다. 결과 : 말초혈액 CD4+ 림프구 중 IFN-γ만을 생성하는 Th1 림프구의 비율은 6.18 ±5.28% (평균±표준편차)였다. 말초혈액 CD4+ 림프구 중 IL-4만을 생성하는 Th2 림프구의 비율은 0.92 ±0.93%였다. 말초혈액 CD8+ 림프구 중 IFN-γ만을 생성하는 Tc1 림프구의 비율은 22.16 ±17.03%였다. 말초혈액 CD8+ 림프구 중 IL-4만을 생성하는 Tc2 림프구의 비율은 0.32 ±0.06%였다. 말초혈액에서의 Th1/Th2비와 Tc1/Tc2 비는 각각 7.41 ±4.38과 166.25 ±43.13이었다. 결론 : 정상인 말초혈액에서의 Th1 림프구의 비율은 Th2 림프구의 비율에 비해 약 7.4배였다. 정상인 말초혈액에서 Tc2 림프구는 거의 관찰되지 않았으며, 대부분의 CD8+ 림프구는 Tc1 림프구로 구성되어 있었다. Purpose : In this study, the frequencies of T helper and cytotoxic cell subsets were observed in peripheral blood CD4- or CD8-positive cells from 20 healthy adults and from this data. Tc1/Tc2 ratios as well as Th1/Th2 ratios were obtained. Methods : Using a multiparameter flow cytometric assay that allows simultaneous determination of intracellular IFN-γ and IL-4 in CD4+ or CD8+ cells, we have studied the emergence of Th (Th1 and Th2) and Tc (Tc1 and Tc2) cell subsets in peripheral bloods of 20 healthy adults. Results : The frequencies of IFN-γ-producing cells in CD4+ populations were 6.18±5.28%(mean ± SD). The frequencies of IL-4-producing cells in CD4+ populations were 0.92 ±0.93%. The frequencies of IFN-γ-producing cells in CD8+ populations were 22.16 ±17.03%. The frequencies of IL-4-producing cells in CD8+ populations 0.32 ±0.06%. The Th1/Th2 and Tc1/Tc2 ratios were 7.41 ±4.38 and 166.25 ±43.13, respectively. Conclusion : The frequencies of Th1 cells were about 7.4 times higher than those Th2 cells in peripheral bloods of healthy adults. because Tc2 cells were hardly observed, almost all of CD8+ cells in peripheral bloods from healthy adults were Tc1 cells.

Dendritic Cell-Mediated Th2 Immunity and Immune Disorders

Kumar, Sunil,Jeong, Yideul,Ashraf, Muhammad Umer,Bae, Yong-Soo MDPI 2019 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.20 No.9

<P>Dendritic cells (DCs) are the professional antigen-presenting cells that recognize and present antigens to naïve T cells to induce antigen-specific adaptive immunity. Among the T-cell subsets, T helper type 2 (Th2) cells produce the humoral immune responses required for protection against helminthic disease by activating B cells. DCs induce a Th2 immune response at a certain immune environment. Basophil, eosinophil, mast cells, and type 2 innate lymphoid cells also induce Th2 immunity. However, in the case of DCs, controversy remains regarding which subsets of DCs induce Th2 immunity, which genes in DCs are directly or indirectly involved in inducing Th2 immunity, and the detailed mechanisms underlying induction, regulation, or maintenance of the DC-mediated Th2 immunity against allergic environments and parasite infection. A recent study has shown that a genetic defect in DCs causes an enhanced Th2 immunity leading to severe atopic dermatitis. We summarize the Th2 immune-inducing DC subsets, the genetic and environmental factors involved in DC-mediated Th2 immunity, and current therapeutic approaches for Th2-mediated immune disorders. This review is to provide an improved understanding of DC-mediated Th2 immunity and Th1/Th2 immune balancing, leading to control over their adverse consequences.</P>

Oxazolone-induced atopic dermatitis murine model shifts from a Th2-dominant response in early challenge into a Th1-elevated response after repetition

( Solam Lee ),( Beom Jun Kim ),( Eun Jung Kim ),( Hyun Ji Hwang ),( Joon Hyung Sohn ),( Chang Ook Park ),( Eung Ho Choi ) 대한피부과학회 2018 대한피부과학회 학술발표대회집 Vol.70 No.2

Background: Oxazolone (Ox)-induced atopic dermatitis (AD) murine model shows immunological and biochemical changes similar to those of AD. However, the alteration in the Th1/Th2 balance during the repeated applications was poorly studied. Objectives: To investigate Th1/Th2 profile exhibited in T-cell subsets and the Th1/Th2-related cytokines during the repeated challenge of Ox. Methods: Ten mice were sensitized by 1% Ox. A week later, five of them were challenged by 0.1% Ox and sacrificed after 12 hours. The others were repeated the challenge every other day for 4 weeks and sacrificed. The differences in Th1 and Th2 subset in skin, spleen and lymph nodes using flow cytometry and Th1- and Th2-related cytokines in serum and skin were investigated. Results: The ratio in Th1/Th2 cell number was lower in first (1-week) challenge than 5-week challenge (0.62 vs. 2.82 in skin, 1.42 vs. 8.53 in lymph node, 2.86 vs. 16.56 in spleen). The ratio in IL-2/IL-5 (0.20 vs. 1.01 in serum and 0.83 vs. 1.51 in skin), IL-2/IL-10 (0.56 vs. 1.35 in serum and 0.24 vs. 1.04 in skin) and IL-2/IL-13 (0.10 vs. 0.09 in serum and 0.06 vs. 0.32 in skin) was lower in 1-week. Conclusion: Ox-induced AD murine model showed the greater Th2 proportion even in first challenge. Repeated challenges increased Th1 immune response relatively, showing that Ox-induced AD murine model has typical immunologic response similar to AD even after first challenge and comparable change to chronic AD following repetition.

Anti-proliferative Activity of T-bet

오연지,신지현,원희연,황은숙 대한면역학회 2015 Immune Network Vol.15 No.4

T-bet is a critical transcription factor that regulates differentiation of Th1 cells from CD4+ precursor cells. Since T-bet directly binds to the promoter of the IFN-γ gene and activates its transcription, T-bet deficiency impairs IFN-γ production in Th1 cells. Interestingly, T-bet-deficient Th cells also display substantially augmented the production of IL-2, a T cell growth factor. Exogenous expression of T-bet in T-bet deficient Th cells rescued the IFN-γ production and suppressed IL-2 expression. IFN-γ and IL-2 reciprocally regulate Th cell proliferation following TCR stimulation. Therefore, we examined the effect of T-bet on Th cell proliferation and found that T-bet deficiency significantly enhanced Th cell proliferation under non-skewing, Th1-skewing, and Th2-skewing conditions. By using IFN-γ-null mice to eliminate the anti-proliferative effect of IFN-γ, T-bet deficiency still enhanced Th cell proliferation under both Th1- and Th2-skewing conditions. Since the anti-proliferative activity of T-bet may be influenced by IL-2 suppression in Th cells, we examined whether T-bet modulates IL-2-independent cell proliferation in a non-T cell population. We demonstrated that T-bet expression induced by ecdysone treatment in human embryonic kidney (HEK) cells increased IFN-γ promoter activity in a dose dependent manner, and sustained T-bet expression considerably decreased cell proliferation in HEK cells. Although the molecular mechanisms underlying anti-proliferative activity of T-bet remain to be elucidated, T-bet may directly suppress cell proliferation in an IFN-γ- or an IL-2-independent manner.

전통사상적 관점에서 본 2·28민주운동 결의문의 정신과 의미

최병덕 재단법인 대구경북연구원 2021 대구경북연구 Vol.20 No.1

As the Anniversary of the February 28th Democracy Movement, the Start of the Democracy movement in the Republic of Korea, to resist corruption and oppression by the Liberal Party, was designated as a National Memorial Day in 2018, the historical value of the February 28th Democracy Movement was officially recognized. The task left for us now is to enhance, remember, celebrate, and inherit the value of the February 28th Democracy Movement and to make it embodied in the present spirit and values. With this background in mind, this study attempts to analyze the resolutions of the February 28th Democracy Movement from a traditional korean thought perspective. Furthermore, I try to analyze the slogans shouted from the February 28th Democracy Movement, interviews of the leaders of the February 28th Democracy Movement, and various records left by them in order to broaden our understanding of the spirit and meaning. Although the resolutions of the February 28th Democracy Movement can be linked with various elements of traditional korean thought, this study attempts to analyze the resolutions of the February 28th Democracy Movement through the practical ethics of Confucian idea, righteousness and progressiveness. Righteousness is to pursue continuous self-reform by recognizing the right principles of human beings, and to realize what is reasonable in concrete reality by a sense of social criticism. Progressiveness is to pursue reform according to the situation of the times, to lead public opinion to solve social problems, and to promote new changes first. From a viewpoint of traditional korean thought, the February 28th Democracy Movement was to express a practice of rightousness that is pursuing moral legitimacy and criticizing what is not right and a sprit of reformation and creativity which opens a new era by taking the lead in solving social evils. Inheriting the spirit of the February 28th Democracy Movement is to realizing social justice first that fits our times in our local community. 자유당의 부정선거와 폭압에 저항한 대한민국 최초의 민주화운동인 2·28민주운동 기념일이 국가기념일로 지정되면서 2·28민주운동의 역사적 가치가 공식적으로 인정되었다. 이제 우리에게 남겨진 과제는 2·28민주운동의 가치를 고양하고 기억하고 기념하고 계승해 나가는 것과 그것이 현재의 정신과 가치로 구현되도록 하는 것이다. 이런 사정을 염두에 두면서 본 연구에서는 2·28민주운동 결의문을 전통사상적 관점에서 살펴본다. 나아가 2·28민주운동에서 외쳐진 구호, 2·28민주운동 주역들의 당시 인터뷰 및 그들이 남긴 각종 기록을 함께 검토해 2·28민주운동이 추구한 정신과 의미에 대한 이해의 폭을 넓히고자 한다. 2·28민주운동 결의문을 전통사상의 다양한 요소와 연결할 수 있지만, 본 연구에서는 2·28민주운동 결의문을 유교 사상의 실천윤리인 올곧음과 나아감을 중심으로 검토한다. 올곧음은 인간의 올바른 도리를 인식하고 동시에 지속적인 자기개혁과 사회비판의식을 가지면서 구체적 현실에서 마땅함을 실현하는 것이며, 나아감은 시대적 상황에 맞게 개혁을 추구하고 사회적 문제를 해결하기 위해 공론을 주도하고 앞장서 새로운 변화를 도모하는 것이다. 전통사상적 관점에서 보았을 때, 2·28민주운동은 도덕적 정당성으로서 올바름을 추구하고 옳지 않은 것을 비판하고 그것에 저항하는 의리 실천 정신이 발현된 것이고 사회적 폐단을 앞장서 해결하여 새로운 시대를 열어가는 수시변통의 경장 정신과 창신의 정신이 발현된 것이었다. 이러한 2‧28민주운동의 정신을 계승하는 것은 우리 시대에 맞는 사회적 정의를 실현하기 위해 우리 지역사회가 앞장서는 것이다.

LincR-PPP2R5C Promotes Th2 Cell Differentiation Through PPP2R5C/PP2A by Forming an RNA–DNA Triplex in Allergic Asthma

Ji Ningfei,Chen Zhongqi,Wang Zhengxia,Sun Wei,Yuan Qi,Zhang Xijie,Jia Xinyu,Wu Jingjing,Jiang Jingxian,Song Meijuan,Xu Tingting,Liu Yanan,Ma Qiyun,Sun Zhixiao,Bao Yanmin,Zhang Mingshun,Huang Mao 대한천식알레르기학회 2024 Allergy, Asthma & Immunology Research Vol.16 No.1

Purpose: The roles and mechanisms of long noncoding RNAs (lncRNAs) in T helper 2 (Th2) differentiation from allergic asthma are poorly understood. We aimed to explore a novel lncRNA, LincR-protein phosphatase 2 regulatory subunit B' gamma (PPP2R5C), in Th2 differentiation in a mouse model of asthma. Methods: LincR-PPP2R5C from RNA-seq data of CD4+ T cells of asthma-like mice were validated and confirmed by quantitative reverse transcription polymerase chain reaction, northern blotting, nuclear and cytoplasmic separation, and fluorescence in situ hybridization (FISH). Lentiviruses encoding LincR-PPP2R5C or shRNA were used to overexpress or silence LincR-PPP2R5C in CD4+ T cells. The interactions between LincR-PPP2R5C and PPP2R5C were explored with western blotting, chromatin isolation by RNA purification assay, and fluorescence resonance energy transfer. An ovalbumin-induced acute asthma model in knockout (KO) mice (LincR-PPP2R5C KO, CD4 conditional LincR-PPP2R5C KO) was established to explore the roles of LincR-PPP2R5C in Th2 differentiation. Results: LncR-PPP2R5C was significantly higher in CD4+ T cells from asthmatic mice ex vivo and Th2 cells in vitro. The lentivirus encoding LincR-PPP2R5C suppressed Th1 differentiation; in contrast, the short hairpin RNA (shRNA) lentivirus decreased LincR-PPP2R5C and Th2 differentiation. Mechanistically, LincR-PPP2R5C deficiency suppressed the phosphatase activity of the protein phosphatase 2A (PP2A) holocomplex, resulting in a decline in Th2 differentiation. The formation of an RNA-DNA triplex between LincR-PPP2R5C and the PPP2R5C promoter enhanced PPP2R5C expression and activated PP2A. LincR-PPP2R5C KO and CD4 conditional KO decreased Th2 differentiation, airway hyperresponsiveness and inflammatory responses. Conclusions: LincR-PPP2R5C regulated PPP2R5C expression and PP2A activity by forming an RNA-DNA triplex with the PPP2R5C promoter, leading to Th2 polarization in a mouse model of acute asthma. Our data presented the first definitive evidence of lncRNAs in the regulation of Th2 cells in asthma.

Ginsenoside Rg1 enhances CD4^(+) T-cell activities and modulates Th1/Th2 differentiation

Lee, Eui-joon,Ko, Eunjung,Lee, Jinwoo,Rho, Samwoong,Ko, Seonggyu,Shin, Min-Kyu,Min, Byung-il,Hong, Moo-Chang,Kim, Si-young,Bae, Hyunsu WHO COLLABORATING CENTRE FOR TRADITIONAL MEDICINE 2003 東西醫學硏究所 論文集 Vol.2003 No.-

Panax ginseng is commonly used as a tonic medicine in Asian countries such as Korea, China, and Japan. It has been reported that ginsenoside Rg1 in P. ginseng increases the proportion of T helper(Th) cells among the total number of T cells and promotes IL-2 gene expression in murine splenocytes. This implies that ginsenoside Rg1 increases the immune activity of CD4 T cells, however, the exact mechanism remains unknown. The present study elucidated the direct effect of Rg1 on helper T-cell activities and on Th1/Th2 lineage development. The results demonstrated that ginsenoside Rg1 had no mitogenic effects on unstimulated CD4^(+) T cells, but augmented CD4^(-) T-cell proliferation upon activation with anti-CD3/anti-CD28 autibodies in a dose-dependent manner. Rg1 also enhanced the expression of cell surface protein CD69 on CD4^(-) T cells. In Th0 condition, ginsenoside Rg1 increases the expression of IL-2 mRNA, and enhances the expression of IL-4 mRNA on CD4^(+) T cells, suggesting that Rg1 prefers to induce Th2 lineage development. In addition, ginsenoside Rg1 increases IL-4 secretion in CD4^(+) T cells under Th2 skewed condition, while decreasing IFN-ysecretion of cells in Th1 polarizing condition. Thus, Rg1 enhances Th2 lineage development from the naive CD4^(+) T cell both by increasing Th2 specific cytokine secretion and by repressing Th1 specific cytokine production. Therefore, these results suggest that ginsenoside Rg1 is a desirable agent for enhancing CD4^(-) T-cell activity, as well as the correction of Th1-dominant pathological disorders.

삼자양친탕(三子養親湯) 물 추출물(抽出物)이 마우스 Th1/Th2 분화 및 알레르기 염증반응 조절에 미치는 효과

박종수,강희,명유진,박성민,심범상,김성훈,최승훈,안규석,Park, Joung-Su,Kang, Hee,Myung, Eu-Gene,Park, Sung-Min,Shim, Bum-Sang,Kim, Sung-Hun,Choi, Seung-Hoon,Ahn, Kyoo-Seok 대한동의생리학회 2006 동의생리병리학회지 Vol.20 No.6

This study was to evaluate the effect of Samjayangchin-tang (STYCT) on mouse Th1 and Th2 cells' differentiation and ovalbumin (OVA)-induced allergic inflammation. The proliferation of mouse CD4 T cells and the secretion of Th1/Th2 cytokines under the influence of STYCT extract were measured as well as the amount of ${\beta}-hexosaminidase$ in RBL-2H3 cells and the levels of $TNF-{\alpha}$ and IL-6 secretion in Raw264.7 cells. BALB/c mice were orally administered with STYCT extract and simultaneously inoculated with OVA to induce allergic reaction and measure the level of total IgE, OVA-specific IgE and the production of IFN- g, IL-4, IL-5 by the spleen cells. When mouse CD4 T cell were stimulated with anti-CO3 and anti-CD28 for 48 hours in various concentrations of STYCT extract, it decreased proliferation of CD4 cells. CD4 T cells under Th1/Th2 polarizing conditions for 3 days with STYCT resulted in mild decrease of IFN- g in Th1 cells and significant decrease of IL-4 in Th2 cells. STYCT extract had a dose-dependent inhibitory effect on antigen-induced release of ${\beta}-hexosaminidase$ in RBL-2H3 cells. Treatment of STYCT extract on LPS stimulated Raw 264.7 cells showed dose-dependent decrease in IL-6 production. Oral administration of STYCT extract on OVA-induced allergic mice showed an inhibitory effect on the levels of total serum IgE and OVA-specific IgE by 53% and 44%, respectively. Culture of spleen cells with OVA resulted in significant increase of IFN- g by 54% and significant decrease of IL-4 and IL-5 by 42%, and 29%, respectively. The results show that STYCT does not strongly induce mouse T cells to transform into Th1 or Th2 but it has an anti-allergic effect in vitro, and that it also corrects the unbalance between the reactions of Th cells in allergic diseases.