Water-Soluble Undenatured Type II Collagen Ameliorates Collagen-Induced Arthritis in Mice

Orie Yoshinari,Yoshiaki Shiojima,Hiroyoshi Moriyama,Junichi Shinozaki,Takahisa Nakane,Kazuo Masuda,Manashi Bagchi 한국식품영양과학회 2013 Journal of medicinal food Vol.16 No.11

Earlier studies have reported the efficacy of type II collagen (C II) in treating rheumatoid arthritis (RA). However, a few studies have investigated the ability of the antigenic collagen to induce oral tolerance, which is defined as active nonresponse to an orally administered antigen. We hypothesized that water-soluble undenatured C II had a similar effect as C II in RA. The present study was designed to examine the oral administration of a novel, water-soluble, undenatured C II (commercially known as NEXT-II) on collagen-induced arthritis (CIA) in mice. In addition, the underlying mechanism of NEXT-II was also identified. After a booster dose (collagen-Freund’s complete adjuvant), mice were assigned to control CIA group, or NEXT-II treatment group, to which saline and NEXT-II were administered, respectively. The arthritis index in the NEXT-II group was significantly lower compared with the CIA group. Serum IL-6 levels in the NEXT-II group were significantly lower compared with the CIA group, while serum IL-2 level was higher. Furthermore, oral administration of NEXT-II enhanced the proportion of CD4 + CD25 + T (Treg) cells, and gene expressions of stimulated dendritic cells induced markers for regulatory T cells such as forkhead box p3 (Foxp3), transforming growth factor (TGF)-b1, and CD25. These results demonstrated that orally administered water-soluble undenatured C II (NEXT-II) is highly efficacious in the suppression of CIA by inducing CD4 + CD25 + Treg cells.

CD2-associated protein/phosphoinositide 3-kinase signaling has a preventive role in angiotensin II-induced podocyte apoptosis

Park, H.Y.,Seong, S.B.,Min, S.Y.,Ha, T.S. Pergamon 2016 The international journal of biochemistry & cell b Vol.79 No.-

Angiotensin II (Ang II) works as a paracrine or autocrine cytokine agent to regulate renal functions and promotes podocytes dysfunction directly or indirectly, causing proteinuria. The glomerular slit diaphragm (SD) serves as a size-selective barrier and is linked to the actin-based cytoskeleton by adaptor proteins, including CD2-associated protein (CD2AP). Therefore, damages to CD2AP affect not only the function of the SD, but also directly disrupt the podocyte cytoskeleton, leading to proteinuria. In addition, CD2AP can facilitate the nephrin-induced phosphoinositide 3-kinase (PI3-K)/Akt signaling, which protects podocytes from apoptosis. Here we found that CD2AP staining was located diffusely but predominantly in the peripheral cytoplasm and CD2AP co-localized with nephrin in mouse podocytes; however, Ang II decreased CD2AP staining diffusely and induced a separation from concentrated nephrin. Ang II notably reduced CD2AP expression in time- and concentration-dependent manners, and this was significantly recovered by losartan. Ang II induced podocyte apoptosis in time- and concentration-dependent manners in TUNEL and FACS assays. LY294002, a PI3-K inhibitor, further reduced CD2AP expression and increased podocyte apoptosis, which was augmented by siRNA for CD2AP. Thus, Ang II induces the relocalization and reduction of CD2AP via AT1R, which would cause podocyte apoptosis by the suppression of CD2AP/PI3-K signaling.

Detection of Foreign Antigen-specific $CD4^+Foxp3^+$ Regulatory T Cells by MHC Class II Tetramer and Intracellular CD154 Staining

Choi, Jin Young,Eo, Seong Kug The Korean Association of Immunobiologists 2013 Immune Network Vol.13 No.6

The unrestricted population of $CD4^+Foxp3^+$ regulatory T (Treg) cells, which have been known to control the expression of autoimmune diseases and protective immunity to inflammatory reactions, has led to greater appreciation of functional plasticity. Detecting and/or isolating Ag-specific $CD4^+Foxp3^+$ Tregs at the single cell level are required to study their function and plasticity. In this study, we established and compared both MHC class II tetramer and intracellular CD154 staining, in order to detect $CD4^+Foxp3^+$ Treg specific for foreign Ag in acute and chronic infections with lymphocytic choriomeningitis virus (LCMV). Our results revealed that MHC class II tetramer staining showed a lower detection rate of LCMV $GP_{66-77}$-specific $CD4^+$ T cells because most of MHC class II tetramers were unbound and unstable when combined staining was performed with intracellular cytokines. In contrast, intracellular CD154 staining was revealed to be easier and simple for detecting LCMV $GP_{66-77}$-specific $CD4^+$ T cells, compared to MHC class II tetramer staining. Subsequently, we employed intracellular CD154 staining to detect LCMV $GP_{66-77}$-specific $CD4^+Foxp3^+$ Tregs using $Foxp3^{GFP}$ knock-in mouse, and found that LCMV $GP_{66-77}$-specific $CD4^+Foxp3^+$ Tregs and polyclonal $CD4^+Foxp3^+$ Tregs showed differential expansion in mice infected with LCMV Arms or Cl13 at acute (8 and 13 days pi) and chronic phases (35 days pi). Therefore, our results provide insight into the valuable use of intracellular CD154 staining to detect and characterize foreign Ag-specific $CD4^+Foxp3^+$ Treg in various models.

Detection of Foreign Antigen-specific CD4+Foxp3+ Regulatory T Cells by MHC Class II Tetramer and Intracellular CD154 Staining

Jin Young Choi,Seong Kug Eo 대한면역학회 2013 Immune Network Vol.13 No.6

The unrestricted population of CD4+Foxp3+ regulatory T (Treg) cells, which have been known to control the expression of autoimmune diseases and protective immunity to inflammatory reactions, has led to greater appreciation of functional plasticity. Detecting and/or isolating Ag-specific CD4+Foxp3+ Tregs at the single cell level are required to study their function and plasticity. In this study, we established and compared both MHC class II tetramer and intracellular CD154 staining, in order to detect CD4+Foxp3+ Treg specific for foreign Ag in acute and chronic infections with lymphocytic choriomeningitis virus (LCMV). Our results revealed that MHC class II tetramer staining showed a lower detection rate of LCMV GP66-77-specific CD4+ T cells because most of MHC class II tetramers were unbound and unstable when combined staining was performed with intracellular cytokines. In contrast, intracellular CD154 staining was revealed to be easier and simple for detecting LCMV GP66-77-specific CD4+ T cells, compared to MHC class II tetramer staining. Subsequently, we employed intracellular CD154 staining to detect LCMV GP66-77-specific CD4+Foxp3+ Tregs using Foxp3GFP knock-in mouse, and found that LCMV GP66-77-specific CD4+Foxp3+ Tregs and polyclonal CD4+Foxp3+ Tregs showed differential expansion in mice infected with LCMV Arms or Cl13 at acute (8 and 13 days pi) and chronic phases (35 days pi). Therefore, our results provide insight into the valuable use of intracellular CD154 staining to detect and characterize foreign Ag-specific CD4+Foxp3+ Treg in various models.

Comprehensive Analysis of Epstein-Barr Virus LMP2A-Specific CD8 + and CD4 +T Cell Responses Restricted to Each HLA Class I and II Allotype Within an Individual

Jo Hyeong-A,Hyun Seung-Joo,Hyun You-Seok,Lee Yong-Hun,Kim Sun-Mi,Baek In-Cheol,Sohn Hyun-Jung,Kim Tai-Gyu 대한면역학회 2023 Immune Network Vol.23 No.2

Latent membrane protein 2A (LMP2A), a latent Ag commonly expressed in Epstein-Barr virus (EBV)-infected host cells, is a target for adoptive T cell therapy in EBV-associated malignancies. To define whether individual human leukocyte antigen (HLA) allotypes are used preferentially in EBV-specific T lymphocyte responses, LMP2A-specific CD8+ and CD4+ T cell responses in 50 healthy donors were analyzed by ELISPOT assay using artificial Ag-presenting cells expressing a single allotype. CD8+ T cell responses were significantly higher than CD4+ T cell responses. CD8+ T cell responses were ranked from highest to lowest in the order HLA-A, HLA-B, and HLA-C loci, and CD4+ T cell responses were ranked in the order HLA-DR, HLA-DP, and HLA-DQ loci. Among the 32 HLA class I and 56 HLA class II allotypes, 6 HLA-A, 7 HLA-B, 5 HLA-C, 10 HLA-DR, 2 HLA-DQ, and 2 HLA-DP allotypes showed T cell responses higher than 50 spot-forming cells (SFCs)/5×105 CD8+ or CD4+ T cells. Twenty-nine donors (58%) showed a high T cell response to at least one allotype of HLA class I or class II, and 4 donors (8%) had a high response to both HLA class I and class II allotypes. Interestingly, we observed an inverse correlation between the proportion of LMP2A-specific T cell responses and the frequency of HLA class I and II allotypes. These data demonstrate the allele dominance of LMP2A-specific T cell responses among HLA allotypes and their intra-individual dominance in response to only a few allotypes in an individual, which may provide useful information for genetic, pathogenic, and immunotherapeutic approaches to EBV-associated diseases.

Anion Effects on Crystal Structures of Cd^II Complexes Containing 2,2'-Bipyridine: Photoluminescence and Catalytic Reactivity

Park, Hyun-Min,Hwang, In-Hong,Bae, Jeong-Mi,Jo, Young-Dan,Kim, Cheal,Kim, Ha-Yeong,Kim, Young-Mee,Kim, Sung-Jin Korean Chemical Society 2012 Bulletin of the Korean Chemical Society Vol.33 No.5

Anion effects on structures of $Cd^{II}$ complexes containing 2,2'-bipyridine (2,2'-bpy) ligands have been studied, and compared with $Zn^{II}$-(2,2'-bpy) complexes. For each anion, different structures have been obtained in both $Zn^{II}$-(2,2'-bpy) and $Cd^{II}$-(2,2'-bpy). Polymeric structures of $Cd^{II}$-2,2'-bpy complexes can be produced by hydrogen bonding interactions as shown in $Zn^{II}$-2,2'-bpy complexes. In addition, the bigger size of a $Cd^{II}$ ion gives higher coordination numbers forming variety of structures, and it makes that chlorides can act as bridging ligands to form a one-dimensional structure. The compound $\mathbf{5}$ catalyzed efficiently the transesterification of a variety of esters with methanol, while the rest of the compounds have displayed very slow conversions. In addition, the emission bands of complexes $\mathbf{1}$, $\mathbf{2}$, $\mathbf{4}$, and $\mathbf{6}$ are blue-shifted compared to the corresponding ligand 2,2'-bpy, whereas $\mathbf{3}$ and $\mathbf{5}$ showed the similar emission observed for the ligand.

Cd^II MOFs Constructed Using Succinate and Bipyridyl Ligands: Photoluminescence and Heterogeneous Catalytic Activity

Lee, Myoung Mi,Kim, Ha-Yeong,Hwang, In Hong,Bae, Jeong Mi,Kim, Cheal,Yo, Chul-Hyun,Kim, Youngmee,Kim, Sung-Jin Korean Chemical Society 2014 Bulletin of the Korean Chemical Society Vol.35 No.6

Four $Cd^{II}$ MOFs, $[Cd_2({\mu}-succinate)_2(H_2O)_2]{\cdot}H_2O$ (1A), $[Cd_2({\mu}-succinate)_2({\mu}-4,4^{\prime}-bpy)_2]{\cdot}H_2O$ (1B), $[\{Cd_2({\mu}-succinate)_2\}({\mu}-bpa)_2\{Cd(H_2O)_2\}(NO_3)_2]{\cdot}H_2O$ (2), and $[Cd({\mu}-succinate)({\mu}-bpp)_2]{\cdot}2H_2O$ (3), with various bipyridyl ligands (4,4'-bipyridine (4,4'-bpy), 1,2-bis(4-pyridyl)ethane (bpa), and 1,3-bis(4-pyridyl)propane (bpp)) were prepared, and their structures were determined using X-ray crystallography. The structures and dimensionalities of $Cd^{II}$-(succinate) compounds varied depending on the auxiliary ligands. Heterogeneous catalytic activity for transesterification reactions, photoluminescence and the thermal stabilities of these compounds were also examined.

CD4+ cytotoxic T cells: an emerging effector arm of anti-tumor immunity

Seongmin Jeong,Nawon Jang,Minchae Kim,최일규 생화학분자생물학회 2023 BMB Reports Vol.56 No.3

While CD8+ cytotoxic T cells have long been considered theprimary effector in controlling tumors, the involvement of CD4+“helper” T cells in anti-tumor immunity has been underappreciated. The investigations of intra-tumoral T cells, fueled by therecent advances in genomic technologies, have led to a rethinkingof the indirect role of CD4+ T cells that have traditionallybeen described as a “helper”. Accumulating evidence frompreclinical and clinical studies indicates that CD4+ T cells canacquire intrinsic cytotoxic properties and directly kill varioustypes of tumor cells in a major histocompatibility complex class II(MHC-II)-dependent manner, as opposed to the indirect “helper”function, thus underscoring a potentially critical contributionof CD4+ cytotoxic T cells to immune responses against a widerange of tumor types. Here, we discuss the biological propertiesof anti-tumor CD4+ T cells with cytotoxic capability and highlightthe emerging observations suggesting their more significantrole in anti-tumor immunity than previously appreciated.

Effect of type II collagen extract on immunosuppression induced by methotrexate in rats

Ee-Hwa Kim,Yong-Min Kim,Jung-Ho Suh 한국운동재활학회 2018 JER Vol.14 No.5

Impaired Memory in OT-II Transgenic Mice Is Associated with Decreased Adult Hippocampal Neurogenesis Possibly Induced by Alteration in Th2 Cytokine Levels

Jeon, Seong Gak,Kim, Kyoung Ah,Chung, Hyunju,Choi, Junghyun,Song, Eun Ji,Han, Seung-Yun,Oh, Myung Sook,Park, Jong Hwan,Kim, Jin-il,Moon, Minho Korean Society for Molecular and Cellular Biology 2016 Molecules and cells Vol.39 No.8

Recently, an increasing number of studies have focused on the effects of CD4+ T cell on cognitive function. However, the changes of Th2 cytokines in restricted CD4+ T cell receptor (TCR) repertoire model and their effects on the adult hippocampal neurogenesis and memory are not fully understood. Here, we investigated whether and how the mice with restricted CD4+ repertoire TCR exhibit learning and memory impairment by using OT-II mice. OT-II mice showed decreased adult neurogenesis in hippocampus and short- and long- term memory impairment. Moreover, Th2 cytokines in OT-II mice are significantly increased in peripheral organs and IL-4 is significantly increased in brain. Finally, IL-4 treatment significantly inhibited the proliferation of cultured adult rat hippocampal neural stem cells. Taken together, abnormal level of Th2 cytokines can lead memory dysfunction via impaired adult neurogenesis in OT-II transgenic.