scholarly journals Interleukin 27 Signaling in Rheumatoid Arthritis Patients: Good or Evil?

2022 ◽  
Vol 12 ◽  
Author(s):  
Liang Han ◽  
Zhe Chen ◽  
Kun Yu ◽  
Jiahui Yan ◽  
Tingting Li ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Responses ◽  
Current Knowledge ◽  
Biological Effects ◽  
Osteoclast Differentiation ◽  
Animal Experiments ◽  
T Helper ◽  
Th1 Cell ◽  
Interleukin 27 ◽  
Helper Type

The occurrence and development of rheumatoid arthritis (RA) is regulated by numerous cytokines. Interleukin 27 (IL-27) is a soluble cytokine that exerts biological effects by regulating the Janus tyrosine kinase (JAK)/signal transducer and activator of the transcription (STAT) signaling pathway via the IL-27 receptor. IL-27 is known for its pleiotropic roles in modulating inflammatory responses. Previous studies found that IL-27 levels are elevated in RA blood, synovial fluid, and rheumatoid nodules. Cellular and animal experiments indicated that IL-27 exerts multiple regulatory functions in RA patients via different mechanisms. IL-27 inhibits ectopic-like structure (ELS) formation and CD4+ T helper type 2 (Th2) cell, CD4+ T helper type 17 (Th17) cell, and osteoclast differentiation in RA, contributing to alleviating RA. However, IL-27 promotes Th1 cell differentiation, which may exacerbate RA synovitis. Moreover, IL-27 also acts on RA synovial fibroblasts (RA-FLSs) and regulatory T cells (Tregs), but some of its functions are unclear. There is currently insufficient evidence to determine whether IL-27 promotes or relieves RA. Targeting IL-27 signaling in RA treatment should be deliberate based on current knowledge.

scholarly journals Sirolimus ameliorates inflammatory responses by switching the regulatory T/T helper type 17 profile in murine colitis

Immunology ◽  
2013 ◽  
Vol 139 (4) ◽  
pp. 494-502 ◽  
Author(s):  
Hui Yin ◽  
Xiangyong Li ◽  
Bobin Zhang ◽  
Tao Liu ◽  
Baohong Yuan ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
T Helper ◽  
Murine Colitis ◽  
Helper Type

scholarly journals Mast Cells Stimulated with Peptidoglycan from Staphylococcus aureus Augment the Development of Th1 Cells

2018 ◽  
Vol 21 ◽  
pp. 296-304
Author(s):  
Katsuhiko Matsui ◽  
Saeko Kanai ◽  
Manami Ikuta ◽  
Saki Horikawa
Keyword(s):  
Staphylococcus Aureus ◽  
Mast Cells ◽  
Chronic Inflammation ◽  
Cell Development ◽  
Th1 Cells ◽  
T Helper ◽  
Th1 Cell ◽  
Th Cells ◽  
Th2 Cell ◽  
Helper Type

Background: The skin of patients with atopic dermatitis (AD) is superficially colonized by Staphylococcus aureus. We have previously found that percutaneous permeation of peptidoglycan (PEG) from S. aureus increases the number of mast cells in the dermis, as seen in skin lesions of AD patients. The purpose of the present study was to clarify the influence of PEG on T helper type 1 (Th1)/ T helper type 2 (Th2) cell development mediated by mast cells. Methods: Mast cells were induced by long-term culture of murine spleen cells in medium supplemented with tumor necrosis factor (TNF)- a. Ovalbumin (OVA) peptide-pulsed mast cells were incubated with naïve Th cells in the presence or absence of PEG. Five days later, Th cells in the culture were stimulated with phorbol 12-myristate 13-acetate (PMA) and ionomycin, and Th1/Th2 cytokine production was investigated by enzyme-linked immunosorbent assay. Results: It was confirmed that the mast cells we obtained had surface expression of I-Ad, worked as antigen-presenting cells, and induced Th1 cell and Th2 cell development. The stimulation of mast cells with PEG enhanced the development of Th1 cells but not that of Th2 cells. The increase of Th1 cell development stimulated by PEG was associated with an increase in the expression of Notch ligand Delta 1 in the mast cells. Furthermore, treatment of mast cells with the macrolide antibiotic josamycin suppressed Th1 cell development and this was correlated with a reduction of both Delta 1 expression and interleukin (IL)-12 production in mast cells. Conclusions: Colonization of S. aureus on the lesioned skin of AD patients contributes to not only an increase in the number of mast cells but also Th1 cell development mediated by mast cells in the dermis and subsequent induction of chronic inflammation, which is characterized by up-regulation of the Th1 cytokine, interferon (IFN)- g. Therefore, application of josamycin to the lesional skin of AD patients may provide relief from chronic inflammation mediated by mast cells.

scholarly journals Regulation of T helper type 2 cell differentiation by murine Schnurri-2

2005 ◽  
Vol 201 (3) ◽  
pp. 397-408 ◽  
Author(s):  
Motoko Y. Kimura ◽  
Hiroyuki Hosokawa ◽  
Masakatsu Yamashita ◽  
Akihiro Hasegawa ◽  
Chiaki Iwamura ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Transforming Growth Factor ◽  
Zinc Finger Protein ◽  
Transforming Growth Factor Β ◽  
Cell Receptor ◽  
Th2 Cells ◽  
Marginal Effect ◽  
T Helper ◽  
Th1 Cell ◽  
Helper Type

Schnurri (Shn) is a large zinc finger protein implicated in cell growth, signal transduction, and lymphocyte development. Vertebrates possess at least three Shn orthologues (Shn-1, Shn-2, and Shn-3), which appear to act within the bone morphogenetic protein, transforming growth factor β, and activin signaling pathways. However, the physiological functions of the Shn proteins remain largely unknown. In Shn-2–deficient mice, mature peripheral T cells exhibited normal anti–T cell receptor–induced proliferation, although there was dramatic enhancement in the differentiation into T helper type (Th)2 cells and a marginal effect on Th1 cell differentiation. Shn-2–deficient developing Th2 cells showed constitutive activation of nuclear factor κB (NF-κB) and enhanced GATA3 induction. Shn-2 was able to compete with p50 NF-κB for binding to a consensus NF-κB motif and inhibit NF-κB–driven promoter activity. Thus, Shn-2 plays a crucial role in the control of Th2 cell differentiation by regulating NF-κB function.

scholarly journals Presentation of the candidate rheumatoid arthritis autoantigen aggrecan by antigen-specific B cells induces enhanced CD4+ T helper type 1 subset differentiation

Immunology ◽  
2012 ◽  
Vol 135 (4) ◽  
pp. 344-354 ◽  
Author(s):  
Caroline L. Wilson ◽  
Dominic W. Hine ◽  
Ariel Pradipta ◽  
Jeffrey P. Pearson ◽  
Willem van Eden ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
B Cells ◽  
T Helper ◽  
Helper Type

scholarly journals PHYTOCHEMICALS IN THE TREATMENT OF ARTHRITIS: CURRENT KNOWLEDGE

2020 ◽  
pp. 1-6
Author(s):  
SOURAV BHATTACHARYA ◽  
SUDIP KUMAR MANDAL ◽  
MD. SEMIMUL AKHTAR ◽  
DIPRA DASTIDER ◽  
SIPRA SARKAR ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Chlorogenic Acid ◽  
Proinflammatory Cytokines ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Bone Erosion ◽  
Osteoclast Differentiation ◽  
Joint Inflammation ◽  
Present Review

The objective of the present review is to evaluate the therapeutic potential of phytochemicals against arthritis, which is asymptomatic disorder of chronic joint inflammation followed by swelling and pain. Here, we discussed about the anti-arthritic activity of many phytomolecules such as Norisoboldine, Berberine, Triptolide, Hesperidin Hesperidin, Madecassocide, Hydroxy napthoquinone, Ginsenoside, Cryptotanshinone, Kirenol, Thymoquinone, Chlorogenic acid, Curcumin, Bromelain, Andrographolide and Allicin. These compounds are able to control inflammatory responses, proinflammatory cytokines, osteoclast differentiation and to prevent bone erosion in the joints. In this article, we reviewed anti-arthritic activities of phytichemicals from 2011-2019, using various scientific websites like PubMed, Google Scholar, Science Direct etc. Till date clinical trials conducted with anti-arthritic phytomolecules are very less. Hence, more clinical trials are needed to bring plant molecules as safe and effective anti-arthritic drugs in the market, either alone or in combination with other anti-arthritic agents.

scholarly journals Norfloxacin, a Fluoroquinolone Antibiotic, Inhibits Langerhans Cell-Mediated Th1 and Th2 Cell Development

2019 ◽  
Vol 22 ◽  
pp. 122-130 ◽  
Author(s):  
Katsuhiko Matsui ◽  
Azusa Kashima ◽  
Ayaka Motegi
Keyword(s):  
Topical Application ◽  
Skin Lesions ◽  
Cell Development ◽  
T Helper ◽  
Down Regulation ◽  
Th1 Cell ◽  
Th2 Cell ◽  
Fluoroquinolone Antibiotic ◽  
Th1 And Th2 ◽  
Helper Type

Background: It is widely acknowledged that Langerhans cells (LCs) play a primary role in the polarization of T helper type 1 (Th1) or T helper type 2 (Th2) immune responses. Our aim was to find fluoroquinolone (“new quinolone”) antibiotics that would inhibit LC-mediated Th2 cell development. Methods: Expression of LC surface molecules was investigated using the reverse transcriptase polymerase chain reaction. The effects of fluoroquinolone antibiotics on T-cell immunoglobulin and mucin domain-containing protein (TIM)-4 expression in LCs were examined to predict whether they would inhibit Th2 cell development. Mice were primed via the hind footpad with ovalbumin (OVA) peptide-pulsed LCs that had been treated with a selected fluoroquinolone antibiotic, then 5 days later the cytokine response in popliteal lymph nodes was examined by enzyme-linked immunosorbent assay. Results: Norfloxacin was selected as a candidate inhibitor of Th2 cell development. As expected, OVA peptide-pulsed LCs that had been treated with norfloxacin and injected into the hind footpads of mice inhibited Th2 cell development, as represented by down-regulation of interleukin (IL)-4 production, as well as Th1 cell development, as represented by down-regulation of interferon (IFN)- g production. This additional inhibition of Th1 cell development was accompanied by suppression of CD40 expression in LCs. In addition, Staphylococcus aureus strains isolated from skin lesions of patients with atopic dermatitis (AD) were more susceptible to norfloxacin than to gentamicin. Topical treatment with norfloxacin significantly suppressed the increase in the skin severity score in NC/Nga mice with AD-like skin lesions. This suppressive effect was associated with a decrease in the production of IFN-g and IL-4 in auricular lymph node cells. Conclusions: The present results show that topical application of norfloxacin inhibits the development of AD-like skin lesions in NC/Nga mice. This suggests that topical application of norfloxacin to AD lesions colonized with S. aureus would act on both superficial S. aureus and epidermal LCs, thus possibly inhibiting the development of Th1 and Th2 cells in vivo, and controlling the severity of AD.

scholarly journals Deficiency in the Transcription Factor Interferon Regulatory Factor (Irf)-2 Leads to Severely Compromised Development of Natural Killer and T Helper Type 1 Cells

2000 ◽  
Vol 192 (3) ◽  
pp. 325-336 ◽  
Author(s):  
Michael Lohoff ◽  
Gordon S. Duncan ◽  
David Ferrick ◽  
Hans-Willi Mittrücker ◽  
Susi Bischof ◽  
...  
Keyword(s):  
Natural Killer ◽  
Leishmania Major ◽  
Nk Cell ◽  
Regulatory Element ◽  
Cell Development ◽  
T Helper ◽  
Regulatory Factor ◽  
Th1 Cell ◽  
Helper Type

Interferon (IFN) regulatory factor (IRF)-2 was originally described as an antagonist of IRF-1–mediated transcriptional regulation of IFN-inducible genes. IRF-1−/− mice exhibit defective T helper type 1 (Th1) cell differentiation. We have used experimental leishmaniasis to show that, like IRF-1−/− mice, IRF-2−/− mice are susceptible to Leishmania major infection due to a defect in Th1 differentiation. Natural killer (NK) cell development is compromised in both IRF-1−/− and IRF-2−/− mice, but the underlying mechanism differs. NK (but not NK+ T) cell numbers are decreased in IRF-2−/− mice, and the NK cells that are present are immature in phenotype. Therefore, like IRF-1, IRF-2 is required for normal generation of Th1 responses and for NK cell development in vivo. In this particular circumstance the absence of IRF-2 cannot be compensated for by the presence of IRF-1 alone. Mechanistically, IRF-2 may act as a functional agonist rather than antagonist of IRF-1 for some, but not all, IFN-stimulated regulatory element (ISRE)-responsive genes.

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