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.

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.

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.

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.

반복 유산 및 착상실패를 보이는 환자에서 Th1 면역반응에 대한 연구

한애라,양광문,곽영희,Han, Ae-Ra,Yang, Kwang-Moon,KwakKim, Joanne 대한생식의학회 2010 Clinical and Experimental Reproductive Medicine Vol.37 No.3

목 적: 반복적 유산 또는 반복적 착상실패 환자의 T 림프구의 Th1 면역반응 정도를 알아보고, T 림프구 활성 정도를 분석하고자 하였다. 연구방법: 반복적 유산 및 반복적 착상실패를 경험한 37명의 환자를 연구군으로 설정하고, 유산이나 불임의 병력이 없이 정상분만의 경력이 있는 11명의 가임 여성을 대조군으로 모집하였다. 유세포분석기를 이용하여, 이들의 말초혈액 중 T helper 세포 내 TNF-$\alpha$와 INF-$\gamma$ 및 IL-10의 발현도를 측정하고 Th1/Th2 세포 비율 (TNF-$\alpha$/IL-10 및 INF-$gamma$/IL-10 발현도)을 계산하여 Th1 면역반응의 우세 정도 및 T 림프구의 활성도를 분석하였으며, 활성 표지자인 CD154와 CD69 발현 정도를 비교하였다. 결 과: 연구군의 평균연령은 $35.3{\pm}4.3$세였으며, 이들에서 T helper cell 내 TNF-$\alpha$/IL-10의 발현 비율이 대조군에 비해 유의하게 높았고 ($42.1{\pm}2.3$ vs. $28.7{\pm}2.7$, p=0.002), CD154와 CD69의 발현율 또한 대조군에 비해 전반적으로 높았다. CD154의 경우, T helper cell ($1.7{\pm}0.5$ vs. $0.3{\pm}0.2$, p=0.038)과 T suppressor cell ($0.6{\pm}0.2$ vs. $0.1{\pm}0.0$, p=0.024) 모두에서 유의하게 높은 발현을 보인 반면, CD69의 경우, 전체 T 림프구 ($5.6{\pm}1.9$ vs. $1.3{\pm}5.4$, p=0.046)와 T suppressor cell ($4.8{\pm}1.3$ vs. $1.8{\pm}0.2$, p=0.035)에서 통계적으로 높은 발현을 확인할 수 있었다. 결 론: 반복적 유산 및 반복적 착상실패를 보이는 여성에서 T 림프구의 활성도와 Th1 면역반응이 증가하였으며 이는, 이들 여성에서 활성화된 T 림프구가 Th1 면역반응을 유도하여 초기 임신의 유지와 착상에 좋지 않은 영향을 미치기 때문으로 생각된다. Objective: To evaluate whether T helper 1 (Th1) immune response is predominant in women with reproductive failures (recurrent spontaneous abortion and recurrent implantation failure) and the activation of T cell is related to Th1 propensity. Methods: Women with a history of recurrent implantation failure or recurrent spontaneous abortion comprise the study group (n=37). Controls are normal fertile women without a history of infertility or pregnancy losses (n=11). Th1/Th2 ratios of interferon (INF)-$\gamma$/interleukin (IL)-10 and tumor necrosis factor (TNF)-$\alpha$/IL-10 expression on $CD3^+/4^+$ cells, CD154, and CD69 expression on T cells are measured by flow cytometric analysis. Results: The ratios of TNF-$\alpha$ to IL-10 expressing on $CD3^+/4^+$ cells (Th1/Th2 cell ratios) are significantly higher in study group ($42.1{\pm}2.3$) as compared with that of controls ($28.7{\pm}2.7$) (p=0.002). The overall trend of CD154 and CD69 expression on T cells are elevated in study group than those of controls. The proportion (%) of $CD3^+/4^+/154^+$ cells ($1.7{\pm}0.5$ vs. $0.3{\pm}0.2$, p=0.038) and the % of $CD3^+/8^+/154^+$ cells ($0.6{\pm}0.2$ vs. $0.1{\pm}0.0$, p=0.024) are significantly higher in study group. The % of $CD3^+/69^+$ cells ($5.6{\pm}1.9$ vs. $1.3{\pm}5.4$, p=0.046) and % of $CD3^+/8^+/69^+$ cells ($4.8{\pm}1.3$ vs. $1.8{\pm}0.2$, p=0.035) among $CD3^+/8^+$ cells are significantly increased in study group. Conclusion: Women with reproductive failures have Th1 propensity with increased T cell activation. These finding means that activated T cell has a harmful effect on early pregnancy and implantation by induction of Th1 immunity.

YinYang1 deficiency ameliorates joint inflammation in a murine model of rheumatoid arthritis by modulating Th17 cell activation

Kwon, Jeong-eun,Lee, Seon-Yeong,Seo, Hyeon-Beom,Moon, Young-Mee,Ryu, Jun-Geol,Jung, Kyung-Ah,Jhun, Joo-Yeon,Park, Jin-Sil,Hwang, Soo-Seok,Kim, Joo-Myeong,Lee, Gap Ryol,Park, Sung-Hwan,Cho, Mi-La Elsevier 2018 Immunology letters Vol.197 No.-

<P><B>Abstract</B></P> <P>Yin Yang 1 (YY1) is a ubiquitously expressed transcription factor that functions in cooperation with various cofactors to regulate gene expression. In the immune system, YY1 enhances cytokine production and T helper (Th) 2 effector cell differentiation, resulting in the activation of inflammation. However, no studies have reported the role of YY1 in Th17 cell regulation, which is implicated in rheumatoid arthritis (RA). We investigated the expression of YY1 in Th17 cells <I>in vitro</I> and revealed increased levels of YY1 mRNA and protein. To elucidate the function of YY1 pathogenesis in RA, we used a collagen-induced arthritis (CIA) mouse model with YY1 deficiency. Deficiency of YY1 reduced the severity of arthritis and joint destruction. Moreover, Th17 cells were dramatically reduced in YY1-deficient mice. The cytokine interleukin (IL)-17 was decreased in YY1-deficient CD4+ T cells <I>ex vivo</I> and <I>in vivo</I>. Interestingly, the level of signal transducer and activator of transcription 3 (STAT3), tumor necrosis factor-α, IL-17, IL-6, and IL-1β were markedly decreased in YY1-deficient mice with CIA. The cytokine-inducing function of YY1 was more specific to IL-17 than to interferon-γ. YY1 plays a role in Th17 cell differentiation and RA pathogenesis. Our findings suggest that future RA therapies should target the regulatory mechanism involved in Th17 cell differentiation, in which YY1 may cooperate with the STAT3 signaling pathway.</P> <P><B>Highlights</B></P> <P> <UL> <LI> YY1 as new target for RA therapies involved in Th17 cell differentiation. </LI> </UL> </P>

중강도 운동이 1형 알레르기와 우울성향을 지닌 중학생의 Th Cytokines 및 IgE에 미치는 영향

오광훈,김정수,유영춘 한국운동생리학회(구 한국운동과학회) 2013 운동과학 Vol.22 No.4

본 연구의 목적은 1형 알레르기 증상과 우울성향을 지닌 중학교 학생들을 대상으로 중강도 운동이 Thcytokines 및 IgE에 미치는 영향을 탐색해 보고자 하였다. 본 실험은 1형 알레르기 질환과 높은 우울성향을 지니고 있는 학생들25명을 최종 대상으로 하였으며, 무작위로 유산소 운동군(n=9), 저항 운동군(n=8), 통제군(n=8)으로 각각 그룹을 나누었다. 12주 동안의 실험기간동안 유산소 운동군은 %HRR의 50~70 % 강도의 중강도 유산소 운동을 30~40분간 실시하였으며, 저항운동군은 세라밴드를 이용한 근력 운동을 실시하였고, 통제군은 일상생활을 유지하도록 하였다. 운동 프로그램 전, 후 혈청 내 면역글로불린E(IgE), Th1(IFN-γ), Th2(IL-4), Treg(TGF-β1) cytokine, CRP와 우울성향검사를 실시하였다. 12주간의 운동프로그램 후 대상자의 자각증상은 유산소 운동군과 저항 운동군에서 개선되었으며, 통제군에서는 특별한 변화가 나타나지 않았다. 혈청 IgE 수준은 유산소운동군(p<.001)과 저항 운동군(p<.01)에서 각각 유의하게 감소하였으나, 통제군에서는 증가하는 양상을 보였다. IFN-γ는 유산소운동군(p<.01)과 저항 운동군(p<.05)에서 각각 유의하게 증가하였으나, 통제군에서는 변화가 나타나지 않았다. IL-4는 검출되지 않았으며, TGF-β1은 세 군 모두에서 증가하고 IFN-γ와 유의한 정적 상관이 나타났지만, 연구와 관련된 특별한 의미가 나타나지 않았다. CRP는 유산소 운동군과 저항운동군에서 감소, 통제군에서는 증가하였지만 통계적으로 유의하지는 않았다. 우울성향은유산소 운동군(p<.01)과 저항운동군(p<.001)에서 통제군에 비해 각각 유의하게 감소되었으며, IgE 수준과 유의한 정적 상관을 나타냈다(p<.05). 이와 같은 사실을 종합해 볼 때 중강도 운동은 알레르기 질환과 우울성향을 동시에 완화시킬 수 있는 효과적인 중재도구로서의 가치가 충분하다는 사실을 알 수 있었다. The purpose of this research is to demonstrate the positive effects of moderate exercise on the changes of Th cytokines and IgE of middle school students with type 1 allergic symptoms and depressive tendency. All the subjects had type 1 allergic symptoms, depressive tendency and had a sedentary lifestyle. They were divided into three groups, moderate aerobic exercise group(AEG; n=9), resistance exercise group(REG; n=8) and control group(CG; n=8) for 12 week`s training. Immunoglobulin E, Th1(IFN-γ), Th2(IL-4), Treg(TGF-β1) cytokine, CRP in serum and depressive tendency were analysed before and after exercise session. After 12 weeks of exercise session, a self-reported subjective symptom was changed positively in AEG and REG, but CG showed no changes. Serum IgE decreased significantly in AEG(p<.001) and REG(p<.01), but CG increased and IFN-γ increased significantly in AEG(p<.01) and REG(p<.05) but CG showed no differences. IL-4 was not detected and TGF-β1 increased in three groups and had a pos itive correlation with IFN-γ, but showed no specific relationship with this research. CRP decreased in AEG and REG, increased in CG with no statistical significance. Depressive tendency decreased significantly in AEG(p<.01) and REG(p<.001) compared to CG and had a significant correlation with IgE(p<.05). These results suggest that moderate exercise is effective to reduce allergic symptoms and depressive tendency simultaneously.

Changes in the Th1:Th2 Cytokine Balance During pregnancy at the Maternal-conceptus Interface in Pigs

Jisoo Han,Inkyu Yoo,Hwanhee Jang,Soogil Chae,Soohyung Lee,Hakhyun Ka 한국동물생명공학회(구 한국동물번식학회) 2017 Reproductive & Developmental Biology(Supplement) Vol.41 No.2

It has been established that a shift from the T helper 1 (Th1) cytokine profile to the T helper 2 (Th2) profile during pregnancy contributes to the successful pregnancy. Interleukin-12 (IL12) is a Th1 cytokine composed of IL12A and IL12B and activates the JAK-STAT pathway and promotes Th1 cell development by binding heterodimeric receptors, IL12RB1 and IL12RB2. Interleukin-10 (IL10), a well-known Th2 cytokine, regulates the expression of Th1 cytokines, MHC class II antigens, and co-stimulatory molecules on immune cells via heterotetramer receptor composed of IL10RA and IL10RB. Although the Th1:Th2 cytokine balance for the maintenance of pregnancy is well studied in humans and rodents, expression and function of IL12 and IL10 are not fully understood in pigs. Thus, this study determined expression of IL12, IL10 and their receptors at the maternal-conceptus interface in pigs. Real-time RT-PCR analysis showed levels of IL12A and IL12B mRNAs in the uterine endometrium were high during early pregnancy, but maintained low expression levels thereafter. Levels of IL12RB1 mRNA during pregnancy showed a biphasic pattern with the highest levels on D15 and D60 of pregnancy, while levels of IL12RB2 mRNA did not change during pregnancy. Levels of IL10 mRNA in the uterine endometrium were highest on D15 of pregnancy and decreased toward term pregnancy. Levels of IL10RA mRNA showed highest levels on D30, while levels of IL10RB mRNA were biphasic with highest levels on D12 and D30 of pregnancy. Immunohistochemical analysis showed that IL12 protein was localized specifically to scattered cell types in endometrial stroma during the estrous cycle and early pregnancy. IL10 protein was detected on scattered cells around the blood vessels in the endometrium during early pregnancy, then detected in all endometrial stroma during mid- to late pregnancy. Conceptus and chorioallantoic tissues during pregnancy also expressed IL12, IL10 and their receptors. These results showed that there were changes in IL12 and IL10 expression in the uterine endometrium during pregnancy, suggesting that a shift toward IL10, a Th2 cytokine, over IL12, a Th1 cytokine, occurs at the maternal conceptus interface for the successful establishment of pregnancy in pigs.

BJ-1108, a 6-Amino-2,4,5-trimethylpyridin-3-ol analogue, regulates differentiation of Th1 and Th17 cells to ameliorate experimental autoimmune encephalomyelitis

Kang, Youra,Timilshina, Maheshwor,Nam, Tae-gyu,Jeong, Byeong-Seon,Chang, Jae-Hoon BioMed Central 2017 BIOLOGICAL RESEARCH Vol.50 No.-

<P><B>Background</B></P><P>CD4<SUP>+</SUP> T cells play an important role in the initiation of an immune response by providing help to other cells. Among the helper T subsets, interferon-γ (IFN-γ)-secreting T helper 1 (Th1) and IL-17-secreting T helper 17 (Th17) cells are indispensable for clearance of intracellular as well as extracellular pathogens. However, Th1 and Th17 cells are also associated with pathogenesis and contribute to the progression of multiple inflammatory conditions and autoimmune diseases.</P><P><B>Results</B></P><P>In the current study, we found that BJ-1108, a 6-aminopyridin-3-ol analogue, significantly inhibited Th1 and Th17 differentiation in vitro in a concentration-dependent manner, with no effect on proliferation or apoptosis of activated T cells. Moreover, BJ-1108 inhibited differentiation of Th1 and Th17 cells in ovalbumin (OVA)-specific OT II mice. A complete Freund’s adjuvant (CFA)/OVA-induced inflammatory model revealed that BJ-1108 can reduce generation of proinflammatory Th1 and Th17 cells. Furthermore, in vivo studies showed that BJ-1108 delayed onset of disease and suppressed experimental autoimmune encephalomyelitis (EAE) disease progression by inhibiting differentiation of Th1 and Th17 cells.</P><P><B>Conclusions</B></P><P>BJ-1108 treatment ameliorates inflammation and EAE by inhibiting Th1 and Th17 cells differentiation. Our findings suggest that BJ-1108 is a promising novel therapeutic agent for the treatment of inflammation and autoimmune disease.</P>

Enhanced Rg3 negatively regulates Th1 cell responses

Cho, Minkyoung,Choi, Garam,Shim, Inbo,Chung, Yeonseok The Korean Society of Ginseng 2019 Journal of Ginseng Research Vol.43 No.1

Background: Korean Red Ginseng (KRG; Panax ginseng Meyer) is a widely used medicinal herb known to exert various immune modulatory functions. KRG and one of its purified components, ginsenoside Rg3, are known to possess anti-inflammatory activities. How they impact helper T cell-mediated responses is not fully explored. In this study, we attempted to evaluate the effect of KRG extract (KRGE) and ginsenoside Rg3 on Th1 cell responses. Methods: Using well-characterized T cell in vitro differentiation systems, we examined the effects of KRGE or enhanced Rg3 on the Th1-inducing cytokine production from dendritic cells (DC) and the naïve $CD4^+$ T cells differentiation to Th1 cells. Furthermore, we examined the change of Th1 cell population in the intestine after treatment of enhanced Rg3. The influence of KRGE or enhanced Rg3 on Th1 cell differentiation was evaluated by fluorescence-activated cell sorting, enzyme-linked immunosorbent assay, and quantitative real-time polymerase chain reaction. Results: KRGE significantly inhibited the production level of IL-12 from DCs and subsequent Th1 cell differentiation. Similarly, enhanced Rg3 significantly suppressed the expression of interferon gamma ($IFN{\gamma}$) and T-bet in T cells under Th1-skewing condition. Consistent with these effects in vitro, oral administration of enhanced Rg3 suppressed the frequency of Th1 cells in the Peyer's patch and lamina propria cells in vivo. Conclusion: Enhanced Rg3 negatively regulates the differentiation of Th1 cell in vitro and Th1 cell responses in the gut in vivo, providing fundamental basis for the use of this agent to treat Th1-related diseases.