• Journal of Physiology & Pathology in Korean Medicine
• /
• v.21 no.4
• /
• pp.869-873
• /
• 2007

Methanol extracts of Acorus gramineus Solander(AGS) were found to exhibit immuno-regulatory action in BALB/c mice. Oral administration of AGS increased murine splenic T lymphocytes, especially $T_H$ and $T_C/T_S$ subpopulations were increased significantly. Treatment of AGS exerted strong cytotoxicity against U937 and HL60 human leukemia cells. Also, AGS induced apoptosis of U937 leukemia cells in a dose dependent manner. Nitric oxide(NO) production and iNOS gene expression were also increased in AGS-treated RAW264.7 cells. Treatment of AGS increased the expression of p53 gene and decreased the expression of PCNA protein in cultured U937 cells. These data suggest that AGS are effective on the immuno-regulatory action and anti-cancer properties.

• IMMUNE NETWORK
• /
• v.20 no.4
• /
• pp.34.1-34.8
• /
• 2020

Cryopreservation and thawing of PBMCs are inevitable processes in expanding the scale of experiments in human immunology. Here, we carried out a fundamental study to investigate the detailed effects of PBMC cryopreservation and thawing on transcriptomes. We sorted Tregs from fresh and cryopreserved/thawed PBMCs from an identical donor and performed single-cell RNA-sequencing (scRNA-seq). We found that the cryopreservation and thawing process minimally affects the key molecular features of Tregs, including FOXP3. However, the cryopreserved and thawed sample had a specific cluster with up-regulation of genes for heat shock proteins. Caution may be warranted in interpreting the character of any cluster of cells with heat shock-related properties when cryopreserved and thawed samples are used for scRNA-seq.

• Biomedical Science Letters
• /
• v.27 no.4
• /
• pp.329-333
• /
• 2021

We previously identified that tumor cells genetically modified with a 4-1BBL co-stimulatory molecule had anticancer effects in a CT26 mouse colorectal tumor model. To identify the distinction between immune cells in a mouse tumor model treated with tumor cells genetically modified with 4-1BBL or β-gal, we examined the immune cells in CT26-WT, CT26-βgal, and CT26-4-1BBL tumor bearing mice 21 days after tumor cell administration. The CD8+ T cells population in mice treated with tumor cells genetically modified with 4-1BBL was significantly increased on day 21 compared to that of tumor cells genetically modified with β-gal in the spleen and tumor tissue. The CD4+ T cell population was not different between the two mice groups. The Foxp3+CD25^high CD4 T cell population decreased on day 21 in tumor tissues, but the decrease was not significant. We also found that CD8 T cells had pivotal roles in inhibiting tumor growth by treating mice with ant-CD4 and CD8 antibodies. These results suggest that tumor cells genetically modified with 4-1BBL could inhibit tumor growth by affecting on CD8 T lymphocytes.

• IMMUNE NETWORK
• /
• v.21 no.3
• /
• pp.18.1-18.13
• /
• 2021

TLR signaling is critical for broad scale immune recognition of pathogens and/or danger molecules. TLRs are particularly important for the activation and the maturation of cells comprising the innate immune response. In recent years it has become apparent that several different TLRs regulate the function of lymphocytes as well, albeit to a lesser degree compared to innate immunity. TLR2 heterodimerizes with either TLR1 or TLR6 to broadly recognize bacterial lipopeptides as well as several danger-associated molecular patterns. In general, TLR2 signaling promotes immune cell activation leading to tissue inflammation, which is advantageous for combating an infection. Conversely, inappropriate or dysfunctional TLR2 signaling leading to an overactive inflammatory response could be detrimental during sterile inflammation and autoimmune disease. This review will highlight and discuss recent research advances linking TLR2 engagement to autoimmune inflammation.

• Korean Journal of Medicinal Crop Science
• /
• v.12 no.4
• /
• pp.315-320
• /
• 2004

The purpose of this research was to investigate the effect of Orostachys japonicus A. Berger (OJB) on the immune system. Administration of OJB (500 mg/kg) enhanced viability of splenocytes and thymocytes in BALB/c mice, and also OJB increased of splenic T lymphocytes, significantly, increased CD4 positive $T_H$ cells and CD8 positive Tc cells. OJB markedly, enhanced the production of ${\gamma}-interferon$ in mice serum. OJB accelerated the apoptosis of L1210 and U937 leukemia cells and increased the expression of apoptosis-related ICE, c-myc, p53 gene. These results suggest that OJB have an immuno-regulatory and anti-cancer activity.

• IMMUNE NETWORK
• /
• v.23 no.1
• /
• pp.5.1-5.28
• /
• 2023

Th cell lineage determination and functional specialization are tightly linked to the activation of lineage-determining transcription factors (TFs) that bind cis-regulatory elements. These lineage-determining TFs act in concert with multiple layers of transcriptional regulators to alter the epigenetic landscape, including DNA methylation, histone modification and threedimensional chromosome architecture, in order to facilitate the specific Th gene expression programs that allow for phenotypic diversification. Accumulating evidence indicates that Th cell differentiation is not as rigid as classically held; rather, extensive phenotypic plasticity is an inherent feature of T cell lineages. Recent studies have begun to uncover the epigenetic programs that mechanistically govern T cell subset specification and immunological memory. Advances in next generation sequencing technologies have allowed global transcriptomic and epigenomic interrogation of CD4+ Th cells that extends previous findings focusing on individual loci. In this review, we provide an overview of recent genome-wide insights into the transcriptional and epigenetic regulation of CD4+ T cell-mediated adaptive immunity and discuss the implications for disease as well as immunotherapies.

• The Korean Journal of Pain
• /
• v.34 no.4
• /
• pp.463-470
• /
• 2021

Background: Although neuropathic pain is a severe and common pain, its pathophysiology has not been elucidated yet. Studies in recent years have focused on the immune system's role in the pathogenesis of neuropathic pain. The aim of this study was to investigate the role of immunological mechanisms in neuropathic pain and the effect of pregabalin by measuring immunological marker levels in peripheral blood before and after pregabalin treatment in postherpetic neuralgia (PHN) patients with neuropathic pain. Methods: Forty patients diagnosed with PHN were included in the study. CD4, T follicular cells (Tfh: CD4⁺CXCR5⁺PD1⁺), Th17 (CD4⁺CCR6⁺ and CD4⁺IL17A⁺), regulatory T cells (Treg: CD4⁺ CD25⁺foxp3⁺), Th1 (CD4⁺ CXCR3⁺ and CD4⁺ IFN-γ⁺) and Th2 (CD4⁺ IL-4⁺) cell ratios were measured in peripheral blood samples before treatment and after 3 months of treatment. Results: When immunological marker and inflammation parameter levels were compared before and after treatment, the helper T cell ratio (CD3⁺, CD4⁺) was 30.28 ± 12.27% before treatment and 34.93 ± 11.70% after treatment, so there was a statistically significant increase (P = 0.028). Th17 was 4.75 ± 5.02% before treatment and 5.80 ± 3.13% after treatment, and there was a statistically significant increase (P = 0.036). Conclusions: Immunological mechanisms play an essential role in the pathogenesis of neuropathic pain, immunologically based treatment approach will be the critical point of treatment.

• Journal of Periodontal and Implant Science
• /
• v.47 no.5
• /
• pp.292-311
• /
• 2017

Purpose: Beyond the limited scope of non-specific polyclonal regulatory T cell (Treg)-based immunotherapy, which depends largely on serendipity, the present study explored a target Treg subset appropriate for the delivery of a novel epitope spreader Pep19 antigen as part of a sophisticated form of immunotherapy with defined antigen specificity that induces immune tolerance. Methods: Human polyclonal $CD4^+CD25^+CD127^{lo-}$ Tregs (127-Tregs) and $na\ddot{i}ve$ $CD4^+CD25^+CD45RA^+$ Tregs (45RA-Tregs) were isolated and were stimulated with target peptide 19 (Pep19)-pulsed dendritic cells in a tolerogenic milieu followed by ex vivo expansion. Low-dose interleukin-2 (IL-2) and rapamycin were added to selectively exclude the outgrowth of contaminating effector T cells (Teffs). The following parameters were investigated in the expanded antigen-specific Tregs: the distinct expression of the immunosuppressive Treg marker Foxp3, epigenetic stability (demethylation in the Treg-specific demethylated region), the suppression of Teffs, expression of the homing receptors CD62L/CCR7, and CD95L-mediated apoptosis. The expanded Tregs were adoptively transferred into an $NOD/scid/IL-2R{\gamma}^{-/-}$ mouse model of collagen-induced arthritis. Results: Epitope-spreader Pep19 targeting by 45RA-Tregs led to an outstanding in vitro suppressive T cell fate characterized by robust ex vivo expansion, the salient expression of Foxp3, high epigenetic stability, enhanced T cell suppression, modest expression of CD62L/CCR7, and higher resistance to CD95L-mediated apoptosis. After adoptive transfer, the distinct fate of these T cells demonstrated a potent in vivo immunotherapeutic capability, as indicated by the complete elimination of footpad swelling, prolonged survival, minimal histopathological changes, and preferential localization of $CD4^+CD25^+$ Tregs at the articular joints in a mechanistic and orchestrated way. Conclusions: We propose human $na\ddot{i}ve$ $CD4^+CD25^+CD45RA^+$ Tregs and the epitope spreader Pep19 as cellular and molecular targets for a novel antigen-specific Treg-based vaccination against collagen-induced arthritis.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.16 no.2
• /
• pp.267-271
• /
• 2002

The purpose of this research was to investigate the immunoregulatory effect, apoptosis of L 1210 leukemia cells of Comus officinalis Sieb.et Zucc. The proliferation of cultured splenocytes and thymocytes were enhanced by the addition of SSY. Splenic, thymic and mesenteric lymph node-T lymphocytes, especially TH cells was significantly increased in SSY-administered (p.o. for 7 days) mice. SSY treatment induced the apoptosis of L1210 mouse leukemia cells. In addition, SSY accelerated the phagocytic activity and nitric oxide production in peritoneal macrophages. These results suggest that SSY have an immuno-regulatory property and anti-cancer effect.

• Gut and Liver
• /
• v.12 no.6
• /
• pp.664-673
• /
• 2018

Background/Aims: Regulatory dendritic cells (rDCs), which can be induced by mesenchymal stem cells (MSCs), play an important role in inducing and maintaining homeostasis of regulatory T cells and exhibit anti-inflammatory functions. In this study, we investigated whether MSCs could differentiate DCs into rDCs and compared the therapeutic effects of rDCs and MSCs on dextran sodium sulfate (DSS)-induced chronic colitis mice. Methods: Immature DCs (imDCs) and lipopolysaccharide (LPS)-treated mature DCs (mDCs) were co-cultured with MSCs for 48 hours, and then the profiles of surface markers and cytokines and regulatory roles of these DCs for primary splenocytes were analyzed. In addition, the therapeutic effects of MSCs and DCs co-cultured with MSCs were compared in chronic colitis mice. Results: After co-culture of imDCs (MSC-DCs) or LPS-treated mDCs (LPS+MSC-DCs) with MSCs, the expression of CD11c, CD80, CD86, interleukin 6 (IL-6), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), and interferon-${\gamma}$ (IFN-${\gamma}$), was decreased, but that of CD11b, IL-10, and transforming growth factor-${\beta}$ (TGF-${\beta}$) was increased. Furthermore, MSC-DCs and LPS+MSC-DCs induced the expression of CD4, CD25, and Foxp3 in primary splenocytes isolated from mice. In DSS-induced colitis mice, MSCs and MSC-DCs increased colon length, body weight, and survival rate and induced histological improvement. Moreover, in the colon tissues, the expression of IL-6, TNF-${\alpha}$, and IFN-${\gamma}$ decreased, but that of IL-10, TGF-${\beta}$, and Foxp3 increased in the MSC- and MSC-DC-injected groups. Conclusions: Our data suggest that MSCs differentiate DCs into rDCs, which ameliorate chronic colitis. Thus, rDCs stimulated by MSCs may be therapeutically useful for the treatment of chronic inflammatory diseases.