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Methods and compositions for modulating the activity of the interleukin-35 receptor complex

a technology of interleukin-35 receptor and activity regulation, which is applied in the direction of drug compositions, immunoglobulins, peptides against animals/humans, etc., can solve the problems of undesirable effector t cells, relapse of disease, and numerous harmful side effects

Inactive Publication Date: 2012-12-27
ST JUDE CHILDRENS RES HOSPITAL INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, in other situations, such effector T cells are undesirable, e.g., in a graft recipient.
General immunosuppressants must be administered frequently, for prolonged periods of time, and have numerous harmful side effects.
Withdrawal of these drugs generally results in relapse of disease.

Method used

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  • Methods and compositions for modulating the activity of the interleukin-35 receptor complex
  • Methods and compositions for modulating the activity of the interleukin-35 receptor complex
  • Methods and compositions for modulating the activity of the interleukin-35 receptor complex

Examples

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Effect test

example 1

IL-35 Signaling and Suppression Mediated by IL-35 Require the Expression of the IL-35R

Materials and Methods:

[0176]Mice. C57BL / 6 (wild type), CD4.cre, and IL12Rβ2− / − mice were purchased from the Jackson Laboratory. Gp130 floxed knockin mice were provided by Rodger McEver at Oklahoma Medical Research Foundation. gp130 fl×CD4.cre×IL12Rb2− / − were obtained by breeding the three mouse strains listed. All animal experiments were performed in American Association for the Accreditation of Laboratory Animal Care-accredited, specific-pathogen-free facilities in the St. Jude Animal Resource Center following national, state and institutional guidelines. Animal protocols were approved by the St Jude Animal Care and Use Committee.

[0177]Tconv Cell Purification. Teff(CD4+CD25−CD45RBhi) from the spleens and lymph nodes of C57BL / 6 or knockout age-matched gp130.fl×CD4.cre×IL12Rb2− / − mice were positively sorted by FACS. After red blood cell lysis, cells were stained with antibodies against CD4, CD25 and...

example 2

IL-35 Signals Primarily Through Two Different STAT Proteins, STAT1 and STAT4

Materials and Methods:

[0182]Mice. Spleens and lymph nodes from Il12rb1− / − mice were provided by D. Fairweather and J. A. Frisancho (Johns Hopkins University), CD4cre×gp130fl / fl mice were provided by M. Karin and S. Grivennikov (University of California at San Diego), IL27ra− / − mice were provided by C. Hunter and J. Stumhofer (University of Pennsylvania), Stat1− / − mice were provided by A. Satoskar and P. Reville (Ohio State University), and Stat3− / − mice were provided by C. Drake and H.R. Yen (Johns Hopkins University). IL12rb2− / −, Stat4− / −, Rag1− / −, C57BL / 6, B6.PL and Balb / c mice were purchased from the Jackson Laboratory. All animal experiments were performed in American Association for the Accreditation of Laboratory Animal Care-accredited, specific-pathogen-free facilities in the St. Jude Animal Resource Center following national, state and institutional guidelines. Animal protocols were approved by the S...

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Abstract

The receptor for Interleukin 35 (IL-35) is provided. The Interleukin 35 Receptor (IL-35R) comprises a heterodimeric complex of the Interluekin12Rβ2 receptor and the gp130 receptor. Various compositions comprising the IL-35R complex, along with polynucleotides encoding the same and kits and methods for the detection of the same the same are provided. Methods of modulating the activity of IL-35R or modulating effector T cell functions are also provided. Such methods employ various IL-35R antagonists and agonists that modulate the activity of the IL-35R complex and, in some embodiments, modulate effector T cell function. Further provided are methods for screening for IL-35R binding agents and for IL-35R modulating agents. Various methods of treatment are further provided.

Description

FIELD OF THE INVENTION[0001]The present invention relates to methods for regulating T cell function in a subject, particularly effector T cell activity.REFERENCE TO A SEQUENCE LISTING SUBMITTED AS A TEXT FILE VIA EFS-WEB[0002]The official copy of the sequence listing is submitted concurrently with the specification as a text file via EFS-Web, in compliance with the American Standard Code for Information Interchange (ASCII), with a file name of 397057SEQLIST.txt, a creation date of Nov. 16, 2010, and a size of 61 KB. The sequence listing filed via EFS-Web is part of the specification and is hereby incorporated in its entirety by reference herein.BACKGROUND OF THE INVENTION[0003]The immune system provides the human body with a means to recognize and defend itself against microorganisms, viruses, and substances recognized as foreign and potentially harmful. Classical immune responses are initiated when antigen-presenting cells present an antigen to CD4+ T helper (Th) lymphocytes result...

Claims

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Application Information

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IPC IPC(8): A61K38/17C12Q1/68G01N33/53C12N5/10A61P29/00A61P35/00C07K14/715C07K16/18C07H21/04A01K67/027A61K39/00G01N33/566
CPCA01K2217/05A01K2267/0387A61K2039/505C07K14/7155C12Q2600/158C07K2317/76C12Q1/6883C12Q1/6886C07K16/244A61P29/00A61P35/00C07K16/2866G01N33/505
Inventor VIGNALI, DARIO AACOLLISON, LAUREN W.
Owner ST JUDE CHILDRENS RES HOSPITAL INC
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