Isthmin 1 Is a Secreted Protein Expressed in Skin, Mucosal Tissues, and NK, NKT, and Th17 Cells

Ricardo Valle-Rios; José L. Maravillas-Montero; Amanda M. Burkhardt; Cynthia Martinez; Bettina Alexandra Buhren; Bernhard Homey; Peter Arne Gerber; Octavio Robinson; Peter Hevezi; Albert Zlotnik

doi:10.1089/jir.2013.0137

Harnessing the Therapeutic Potential of Th17 Cells

Mediators of Inflammation ◽

10.1155/2015/205156 ◽

2015 ◽

Vol 2015 ◽

pp. 1-11 ◽

Cited By ~ 20

Author(s):

Jonas Bystrom ◽

Taher E. Taher ◽

M. Sherwan Muhyaddin ◽

Felix I. Clanchy ◽

Pamela Mangat ◽

...

Keyword(s):

Chronic Inflammation ◽

Th17 Cells ◽

Protective Immunity ◽

Drug Target ◽

Therapeutic Potential ◽

Gene Profile ◽

Profile Similarity ◽

Mucosal Tissues ◽

Interleukin 17A ◽

Future Drug

Th17 cells provide protective immunity to infections by fungi and extracellular bacteria as well as cancer but are also involved in chronic inflammation. The cells were first identified by their ability to produce interleukin 17A (IL-17A) and, subsequently, associated with chronic inflammation and autoimmunity. Th17 cells have some gene profile similarity with stem cells and can remain dormant in mucosal tissues for long periods. Indeed, recent studies suggest that functionally distinct subsets of pro- and anti-inflammatory Th17 cells can interchange phenotype and functions. For development, Th17 cells require activation of the transcription factors STAT3 and RORγt while RUNX1, c-Maf, and Aiolos are involved in changes of phenotype/functions. Attempts to harness Th17 cells against pathogens and cancer using vaccination strategies are being explored. The cells gain protective abilities when induced to produce interferonγ(IFNγ). In addition, treatment with antibodies to IL-17 is effective in treating patients with psoriasis, psoriatic arthritis, and refectory rheumatoid arthritis. Moreover, since RORγt is a nuclear receptor, it is likely to be a potential future drug target for modulating Th17 functions. This review explores pathways through which Th17 subsets are induced, the molecular basis of their plasticity, and potential therapeutic strategies for their modulation in diseases.

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Loss and Dysregulation of Th17 Cells during HIV Infection

Clinical and Developmental Immunology ◽

10.1155/2013/852418 ◽

2013 ◽

Vol 2013 ◽

pp. 1-9 ◽

Cited By ~ 46

Author(s):

Sandra L. Bixler ◽

Joseph J. Mattapallil

Keyword(s):

Hiv Infection ◽

Bacterial Translocation ◽

T Helper Cells ◽

Th17 Cells ◽

Mucosal Barrier ◽

Immune Homeostasis ◽

Chronic Immune Activation ◽

T Helper ◽

T Helper 17 ◽

Mucosal Tissues

Bacterial translocation across the damaged mucosal epithelium has emerged as a major paradigm for chronic immune activation observed during HIV infection. T helper 17 (Th17) cells are a unique lineage of T helper cells that are enriched in mucosal tissues and are thought to play a central role in protecting the integrity of the mucosal barrier and maintaining immune homeostasis at mucosal sites. Th17 cells are lost very early during the course of HIV infection, and their loss has been shown to correlate with bacterial translocation. Interestingly, Th17 cells are unable to completely recover from the early destruction even after successful antiretroviral therapy (ART). Here, we review some of the potential mechanisms for the loss and dysregulation of Th17 cells during HIV infection.

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CTRP4 binds to the interleukin-6 Receptor and ameliorates autoimmune encephalomyelitis by suppressing Th17 cell differentiation

10.21203/rs.3.rs-265573/v1 ◽

2021 ◽

Author(s):

Lulu Cao ◽

Wei Chen ◽

Daxiang Na ◽

He Huang ◽

Qi Li ◽

...

Keyword(s):

Th17 Cell ◽

Th17 Cells ◽

Secreted Protein ◽

Autoimmune Encephalomyelitis ◽

Th17 Cell Differentiation ◽

Interleukin 6 Receptor ◽

Receptor Signaling Pathway ◽

Potential Therapeutic Intervention ◽

Experimental Autoimmune

Abstract CTRP4, a secreted protein, plays an important role in protecting against sepsis and energy metabolism; however, its physiological functions in autoimmune disease remain unknown. In this study, we demonstrate that Th17 cell-associated experimental autoimmune encephalomyelitis was greatly exacerbated in Ctrp4−/− mice because of increased Th17 cell infiltration. In vitro, Ctrp4 deficiency enhanced the ability of naïve CD4+ T cells to differentiate into Th17 cells. Mechanistically, CTRP4 interfered with the binding of IL-6 to its receptor IL-6R by directly binding to IL-6R and suppressed the activation of STAT3-related pathways in response to IL-6. Furthermore, treatment of induced EAE mice with recombinant CTRP4 protein ameliorated the symptom. In conclusion, our results indicate that CTRP4, as an endogenous regulator of the IL-6 receptor signaling pathway, may be a potential therapeutic intervention for multiple sclerosis.

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The Effects of Vitamin K1 and Warfarin on Prothrombin Expression in Human Hepatoblastoma (HepG2) Cells

Thrombosis and Haemostasis ◽

10.1055/s-0038-1656315 ◽

1992 ◽

Vol 68 (01) ◽

pp. 040-047 ◽

Cited By ~ 3

Author(s):

C Scott Jamison ◽

Bryan F Burkey ◽

Sandra J Friezner Degen

Keyword(s):

Total Protein ◽

Hepg2 Cells ◽

Enzyme Linked Immunosorbent Assay ◽

Response Analysis ◽

Secreted Protein ◽

Mrna Levels ◽

Vitamin K1 ◽

Maximal Increase ◽

Protein Levels ◽

Warfarin Treatment

SummaryCultures of human hepatoblastoma (HepG2) cells were treated with vitamin K1 or warfarin and prothrombin antigen and mRNA levels were determined. With 3 and 6 h of 10 µg vitamin K1 treatment secreted prothrombin antigen levels, relative to total secreted protein levels, were increased 1.5-fold and 2.1-fold, respectively, over ethanol-treated control levels as determined by an enzyme-linked immunosorbent assay. Dose-response analysis with 3 h of 25 µg/ml vitamin K1 treatment demonstrated a maximal increase of 2.0-fold in secreted prothrombin antigen levels, relative to total secreted protein levels, over ethanol-treated control levels. Pulse-chase analysis with 35S-methionine and immunoprecipitation of 35S-labelled prothrombin demonstrated that, with vitamin K1 treatment (25 µg/ml, 3 h), the rate of prothrombin secretion increased approximately 2-fold and the total amount (intra- and extracellular) of prothrombin synthesized increased approximately 50% over ethanol-treated control levels. Warfarin treatment (1, 5, or 10 µg/ml, 24 h) resulted in decreases in secreted prothrombin antigen levels, relative to total protein levels to approximately 85%, 87% or 81% of ethanol-treated control levels. Analysis of total RNA isolated from these cultures by Northern and solution hybridization techniques demonstrated that prothrombin mRNA was approximately 2.1 kb and that neither vitamin K1 nor warfarin treatment affected the quantity of prothrombin mRNA (ranging from 240–350 prothrombin mRNA molecules per cell). These results demonstrate that vitamin K1 and warfarin, in addition to effects on γ-carboxylation, affect prothrombin synthesis post-transcriptionally, perhaps influencing translation, post-translational processing and/or secretion mechanisms.

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