• IMMUNE NETWORK
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• 제15권2호
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• pp.73-82
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• 2015

Respiratory syncytial virus (RSV) infection is recognized by the innate immune system through Toll like receptors (TLRs) and retinoic acid inducible gene I. These pathways lead to the activation of type I interferons and resistance to infection. In contrast to TLRs, very few studies have examined the role of NOD-like receptors in viral recognition and induction of adaptive immune responses to RSV. Caspase-1 plays an essential role in the immune response via the maturation of the proinflammatory cytokines IL-$1{\beta}$ and IL-18. However, the role of caspase-1 in RSV infection in vivo is unknown. We demonstrate that RSV infection induces IL-$1{\beta}$ secretion and that caspase-1 deficiency in bone marrow derived dendritic cells leads to defective IL-$1{\beta}$ production, while normal RSV viral clearance and T cell responses are observed in caspase-1 deficient mice following respiratory infection with RSV. The frequencies of IFN-${\gamma}$ producing or RSV specific T cells in lungs from caspase-1 deficient mice are not impaired. In addition, we demonstrate that caspase-1 deficient neonatal or young mice also exhibit normal immune responses. Furthermore, we find that IL-1R deficient mice infected with RSV exhibit normal Th1 and cytotoxic T lymphocytes (CTL) immune responses. Collectively, these results demonstrate that in contrast to TLR pathways, caspase-1 might not play a central role in the induction of Th1 and CTL immune responses to RSV.

• 셀메드
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• 제3권1호
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• pp.3.1-3.3
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• 2013

The receptor activator of NF-${\kappa}B$ ligand (RANKL), a member of the tumor necrosis factor ligand family, has extensive functions beyond osteoclast development. RANKL is expressed in many immune cells such as osteoblasts, osteocytes, marrow stromal cells, activated T cells, synovial cells, keratinocytes, and mammary gland epithelial cells as well as in various tissues. The ligation of RANK by RANKL promotes dendritic cells (DCs) survival through prosurvival signals and the up-regulation of the anti-apoptotic proteins Bcl-2 and Bcl-$x_L$ and plays a crucial role in DCs-mediated Th1 differentiation. Therefore, RANKL plays an important role in the regulation of DCs/T cells-mediated specific immunity. This review will briefly inform our current understanding of the role of RANKL signaling in T cells-DCs communication in the immune system.

• Asian-Australasian Journal of Animal Sciences
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• 제32권5호
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• pp.614-628
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• 2019

Objective: The inhibitory leukocyte immunoglobulin-like receptors (LILRBs) play an important role in innate immunity. The present study represents the first description of the cloning and structural and functional analysis of LILRB1 and LILRB3 isolated from two genetically disparate chicken lines. Methods: Chicken LILRB1-3 genes were identified by bioinformatics approach. Expression studies were performed by transfection, quantitative polymerase chain reaction. Signal transduction was analyzed by western blots, immunoprecipitation and flow cytometric. Cytokine levels were determined by enzyme-linked immunosorbent assay. Results: Amino acid homology and phylogenetic analyses showed that the homologies of LILRB1 and LILRB3 in the chicken line 6.3 to those proteins in the chicken line 7.2 ranged between 97%-99%, while homologies between chicken and mammal proteins ranged between 13%-19%, and 13%-69%, respectively. Our findings indicate that LILRB1 and LILRB3 subdivided into two groups based on the immunoreceptor tyrosine-based inhibitory motifs (ITIM) present in the transmembrane domain. Chicken line 6.3 has two ITIM motifs of the sequence LxYxxL and SxYxxV while line 7.2 has two ITIM motifs of the sequences LxYxxL and LxYxxV. These motifs bind to SHP-2 (protein tyrosine phosphatase, non-receptor type 11) that plays a regulatory role in immune functions. Moreover, our data indicate that LILRB1 and LILRB3 associated with and activated major histocompatibility complex (MHC) class I and ${\beta}2-microglobulin$ and induced the expression of transporters associated with antigen processing, which are essential for MHC class I antigen presentation. This suggests that LILRB1 and LILRB3 are transcriptional regulators, modulating the expression of components in the MHC class I pathway and thereby regulating immune responses. Furthermore, LILRB1 and LILRB3 activated Janus kinase2/tyrosine kinase 2 (JAK2/TYK2); signal transducer and activator of transcription1/3 (STAT1/3), and suppressor of cytokine signaling 1 genes expressed in Macrophage (HD11) cells, which induced Th1, Th2, and Th17 cytokines. Conclusion: These data indicate that LILRB1 and LILRB3 are innate immune receptors associated with SHP-2, MHC class I, ${\beta}2-microglobulin$, and they activate the Janus kinase/signal transducer and activator of transcription signaling pathway. Thus, our study provides novel insights into the regulation of immunity and immunopathology.

• Journal of Acupuncture Research
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• 제22권3호
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• pp.23-35
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• 2005

본 연구에서는 전침자극이 면역계의 THl/TH2 분화평형에 미치는 영향과 opioid system 과의 관계를 알아보고자 DNP-KLH의 자극을 통해 IgE 매개 알러지 반응모델을 구축하고 족삼리(足三里).에 전침자극을 가한 후 TH1/TH2 분화평형 및 opioid receptor antagonist인 naloxone에 의 한 반전여부를 확인하기 위해 total IgE, antigen-specific IgE, IFN-${\gamma}$ 및 IL-4 mRNA 발현량을 측정하여 다음과 같은 결과를 얻었다. 1. 전침자극은 DNP-KLH로 인해 과도하게 생산 된 혈청 total IgE 및 antigen-specific IgE를 감소시킴으로서 알러지 반응에 대한 유의한 억제능을 발휘하였으며, naloxone 투여로 전침 의 효과가 상쇠된 것으로 미루어 opioid system이 전침에 의한 항알러지 효과에 중요한 역할을 하는 것으로 추정된다. 2. 또한 전침자극은 DNP-KLH로 인한 TH2 cytokine의 편향상태에 대하여 TH1/TH2 평형조절능을 가진다는 것을 확인하였으며, naloxone으로 반전되지 않는 것으로 미루어 전침이 미치는 보조 T cell 분화에 대한 효과 는 opioid system에 의존하지 않는 것으로 추정된다.

• 한국임상수의학회지
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• 제27권4호
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• pp.311-314
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• 2010

Bartonella henselae 는 고양이할큄병의 원인체이다. 고양이가 Bartonella spp.의 주된 보유숙주이기는 하지만, 최근 애완견의 할큄에 의한 고양이할큄병 발생이 보고되었다. 8두의 개에 1 ml의 인산완충식염수에 부유한 $2{\times}10^8CFU$의 B. henselae Houston-1을 0일에 피내주사하고, 동량을 21, 28, 36, 58, 64일째에 추가로 피내주사 하였다. B. henselae 감염을 nested PCR을 통해 확인하였다. B. henselae-PCR 양성군이 음성군에 비해 B. henselae로 말초혈액단 핵구를 자극한 후 얻은 배양상청액에서의 IFN-$\gamma$ 농도가 유의성 있게 높았다. B. henselae자극시, Th1활성을 보이는 개 말초혈액단핵구의 면역양상은 Th2활성을 보인다고 알려진 고양이와는 다른 것으로 보인다.

• 동의생리병리학회지
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• 제19권1호
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• pp.69-74
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• 2005

In Oriental medicine the primordial Qi and the defensive Qi are considered as important for immunity. Therefore it is anticipated that the improvement of the primordial Qi and the defensive Qi can enhance the ability of immune cells. This experiment was conducted to investigate how Ginseng Radix, Astragali Radix, Atractylodis Rhizoma Alba, Glycyrrhizae Radix, representative of Qi tonifying herbs, affect the immune system in terms of controlling and balancing immune cells. Using the MTS assay, increased proliferations were observed from herbal treated cells, among which Gins-eng showed the highest proliferation. When splenocytes were activated with anti-CD3 plus herbal extracts, levels of IFN-g and IL-4 were increased but those of IL-2 showed little change compared with the control cells. Levels of IL-2, IFN-g and IL-4 were increased in purified CD4 T cells when activated with anti-CD3/anti-CD28 but at $100\;{\mu}g/ml$ of Astragali and Atractylodis, levels of IL-2 were decreased by 11% and 42%, respectively and those of IFN-g were decreased by 55% and 12%, respectively. Under Th1/Th2 polarizing conditions, levels of IFN-g in Th1 cells treated with herbal extracts were all decreased but when it comes to IL-4, its levels were increased in Ginseng and Glycyrrhizae treated cells but decreased in Astragali and Atractylodis treated cells. Taken together, the data show that compared with other qi tonifying herbs, Ginseng and Glycyrrhizae have a tendency to favor Th2 cell differentiation in vitro.

• IMMUNE NETWORK
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• 제21권6호
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• pp.42.1-42.20
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• 2021

Eosinophils play critical roles in the maintenance of homeostasis in innate and adaptive immunity. Although primarily known for their roles in parasitic infections and the development of Th2 cell responses, eosinophils also play complex roles in other immune responses ranging from anti-inflammation to defense against viral and bacterial infections. However, the contributions of pattern recognition receptors in general, and NOD-like receptors (NLRs) in particular, to eosinophil involvement in these immune responses remain relatively underappreciated. Our in vivo studies demonstrated that NLRC4 deficient mice had a decreased number of eosinophils and impaired Th2 responses after induction of an allergic airway disease model. Our in vitro data, utilizing human eosinophilic EoL-1 cells, suggested that TLR2 induction markedly induced pro-inflammatory responses and inflammasome forming NLRC4 and NLRP3. Moreover, activation by their specific ligands resulted in caspase-1 cleavage and mature IL-1β secretion. Interestingly, Th2 responses such as secretion of IL-5 and IL-13 decreased after transfection of EoL-1 cells with short interfering RNAs targeting human NLRC4. Specific induction of NLRC4 with PAM3CSK4 and flagellin upregulated the expression of IL-5 receptor and expression of Fc epsilon receptors (FcεR1α, FcεR2). Strikingly, activation of the NLRC4 inflammasome also promoted expression of the costimulatory receptor CD80 as well as expression of immunoregulatory receptors PD-L1 and Siglec-8. Concomitant with NLRC4 upregulation, we found an increase in expression and activation of matrix metalloproteinase (MMP)-9, but not MMP-2. Collectively, our results present new potential roles of NLRC4 in mediating a variety of eosinopilic functions.

• IMMUNE NETWORK
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• 제3권3호
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• pp.182-187
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• 2003

Background: The mushroom Phellinus linteus (PL) has been shown to have the anti-tumor and immunostimulatory effects. We hypothesized that the hot water extract of PL (WEPL) exerts its significant immunostimulatory effect by inducing production of the Th1-derived cytokine interferon-${\gamma}$ (IFN-${\gamma}$) by T lymphocytes. Methods: T lymphocytes were isolated from the mice fed with 200 mg/kg of WEPL once a day for 4 weeks, and then stimulated with the mitogen concanavaline A (Con A). IFN-${\gamma}$ gene and intracellular protein expressions were analyzed by RT-PCR and flow cytometry, respectively. The production of IFN-${\gamma}$ was measured by enzyme-linked immunosorbent assay. Results: WEPL significantly enhanced the transcription of IFN-${\gamma}$ mRNA. The effect of WEPL on IFN-${\gamma}$ expression was further supported by a concomitant increase in the number of cells with intracellular IFN-${\gamma}$ protein as well as the secretion of IFN-${\gamma}$. However, WEPL did not modulate either gene expression or protein secretion of interleukin-4, a Th2-associated cytokine, by Con A-stimulated T lymphocytes. Conclusion: Our results demonstrate that one of the potentially beneficial anti-tumor and immunostimulatory effects of WEPL may be mediated through the enhancement of IFN-${\gamma}$ secretion by T lymphocytes.

• Food Science and Biotechnology
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• 제18권6호
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• pp.1316-1321
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• 2009

Multiple beneficial properties of Opuntia ficus indica (OPF) are well established. In the present study, we have investigated the immunological role of OPF extract (OPFE) on murine splenocytes. OPFE dose- and time-dependently enhanced the proliferation of splenocytes without cytotoxicity. Our results also showed that the number of $CD4^+$ helper T cells and CD45R/$B220^+$ pan B cells increased markedly, but not $CD8^+$ cytotoxic T cells or $CD11b^+$ granulocytes/macrophages. In addition, OPFE significantly decreased the production levels of T helper (Th) 1 type cytokines, interferon (IFN)-$\gamma$, and tumor necrosis factor (TNF)-$\alpha$, although had no significantly differences in those of interleukin (IL)-4, a Th2 type cytokine in concanavalin A (Con A)-stimulated blastogenic cells. Furthermore, OPFE alone strongly increased IL-4 production and decreased TNF-$\alpha$ production even in the absence of Con A. On the basis of these results, this study suggests that OPFE enhances immunity by regulating the pro- and anti-inflammatory response, indicating that this extract exerts a marked immunomodulatory effect, confirming its usefulness as therapy for immune-related diseases.

• 대한본초학회지
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• 제34권2호
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• pp.41-47
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• 2019

Objectives : A traditional herbal prescription, Kyung-Ok-Ko (KOK), has long been used in oriental medicine as an invigorant for age-related diseases, such as amnesia and stroke. However, the beneficial value of KOK for immune responses is largely unknown. Based on the above mentioned effects of KOK, other previous reports, and its use in traditional medicine, we hypothesized that KOK displays beneficial effects against methotrexate (MTX)-induced immune suppression. Methods : We investigated the effects of KOK (0.6 g/kg/day, oral (p.o.)) on deteriorated immunity caused by MTX (2 mg/kg/day, p.o.) in an immune suppression mouse model. MTX was fed to mice once a day for 7 days. After the immune responses of the mice deteriorated by MTX treatment, KOK in water was fed to the mice once a day for 14 days. We then measured the expression levels of various cytokines, such as T helper cell (Th1, Th2) cytokines, and the number of immune cells, such as spleen T cells, B cells, and macrophages. Results : The data showed that MTX decreased Th1 profiles (interferon $(IFN)-{\gamma}$, interleukin (IL)-2, IL-12) and the number of immune cells, and increased Th2 profiles (IL-4, IL-5, IL-13), which were normalized significantly by post-administration of KOK. However, there was no significant difference in body-weight gain between MTX- and KOK-treated mice. Conclusion : These results indicate that KOK has immune-enhancing functions and reduces immunotoxicity of MTX, suggesting that supplementation with KOK will improve immune responses clinically and be useful for the prevention of immune-related diseases.