Differential expression and function of human IL-12Rβ2 polymorphic variants

Ralf Paus; Roelof A. De Paus; Marije A. Geilenkirchen; Sander Van Riet; Jaap T. Van Dissel; Esther Van De Vosse

doi:10.1016/j.molimm.2013.07.002

Differential expression and function of human IL-12Rβ2 polymorphic variants

Ralf Paus, Roelof A. De Paus, Marije A. Geilenkirchen, Sander Van Riet, Jaap T. Van Dissel, Esther Van De Vosse

Research output: Contribution to journal › Article › peer-review

Abstract

The receptor for interleukin-12, formed by IL-12Rβ1 and IL-12Rβ2, mediates the type I immune responses of various types of lymphocytes. Polymorphisms in IL12RB2, the gene encoding IL-12Rβ2, were reported to be associated with several immune related diseases, such as Crohn's disease. Because the IL23R and IL12RB2 genes are located in close proximity on the genome, the reported associations might also be attributable to linked polymorphisms in IL23R, which were found to be associated with immune related diseases as well. To clarify the role of IL-12Rβ2 in immune diseases, we investigated the functional consequences of thirteen amino acid substitutions in IL-12Rβ2. We developed a model with retroviral expression of IL-12Rβ2 in B cell lines. With the use of this model the expression and function of the variants was compared within the same genetic background. Four of the IL-12Rβ2 variants, N271Y, R313G, A604V and L808R showed reduced IL-12 responses compared to the wild type variant. Two of these are relatively common in some populations and may be used in future association studies to reveal a role for IL-12 in infectious and/or immune related diseases. © 2013 Elsevier Ltd.

Original language	English
Pages (from-to)	380-389
Number of pages	9
Journal	Molecular immunology
Volume	56
Issue number	4
DOIs	https://doi.org/10.1016/j.molimm.2013.07.002
Publication status	Published - 31 Dec 2013

Keywords

Autoimmunity
IL-12
IL-12Rβ2
IL12RB2
Mutation
Polymorphism

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.molimm.2013.07.002

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@article{94b258995f3840168dce7a058b627e83,

title = "Differential expression and function of human IL-12Rβ2 polymorphic variants",

abstract = "The receptor for interleukin-12, formed by IL-12Rβ1 and IL-12Rβ2, mediates the type I immune responses of various types of lymphocytes. Polymorphisms in IL12RB2, the gene encoding IL-12Rβ2, were reported to be associated with several immune related diseases, such as Crohn's disease. Because the IL23R and IL12RB2 genes are located in close proximity on the genome, the reported associations might also be attributable to linked polymorphisms in IL23R, which were found to be associated with immune related diseases as well. To clarify the role of IL-12Rβ2 in immune diseases, we investigated the functional consequences of thirteen amino acid substitutions in IL-12Rβ2. We developed a model with retroviral expression of IL-12Rβ2 in B cell lines. With the use of this model the expression and function of the variants was compared within the same genetic background. Four of the IL-12Rβ2 variants, N271Y, R313G, A604V and L808R showed reduced IL-12 responses compared to the wild type variant. Two of these are relatively common in some populations and may be used in future association studies to reveal a role for IL-12 in infectious and/or immune related diseases. {\textcopyright} 2013 Elsevier Ltd.",

keywords = "Autoimmunity, IL-12, IL-12Rβ2, IL12RB2, Mutation, Polymorphism",

author = "Ralf Paus and {De Paus}, {Roelof A.} and Geilenkirchen, {Marije A.} and {Van Riet}, Sander and {Van Dissel}, {Jaap T.} and {Van De Vosse}, Esther",

year = "2013",

month = dec,

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doi = "10.1016/j.molimm.2013.07.002",

language = "English",

volume = "56",

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journal = "Molecular immunology",

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TY - JOUR

T1 - Differential expression and function of human IL-12Rβ2 polymorphic variants

AU - Paus, Ralf

AU - De Paus, Roelof A.

AU - Geilenkirchen, Marije A.

AU - Van Riet, Sander

AU - Van Dissel, Jaap T.

AU - Van De Vosse, Esther

PY - 2013/12/31

Y1 - 2013/12/31

N2 - The receptor for interleukin-12, formed by IL-12Rβ1 and IL-12Rβ2, mediates the type I immune responses of various types of lymphocytes. Polymorphisms in IL12RB2, the gene encoding IL-12Rβ2, were reported to be associated with several immune related diseases, such as Crohn's disease. Because the IL23R and IL12RB2 genes are located in close proximity on the genome, the reported associations might also be attributable to linked polymorphisms in IL23R, which were found to be associated with immune related diseases as well. To clarify the role of IL-12Rβ2 in immune diseases, we investigated the functional consequences of thirteen amino acid substitutions in IL-12Rβ2. We developed a model with retroviral expression of IL-12Rβ2 in B cell lines. With the use of this model the expression and function of the variants was compared within the same genetic background. Four of the IL-12Rβ2 variants, N271Y, R313G, A604V and L808R showed reduced IL-12 responses compared to the wild type variant. Two of these are relatively common in some populations and may be used in future association studies to reveal a role for IL-12 in infectious and/or immune related diseases. © 2013 Elsevier Ltd.

AB - The receptor for interleukin-12, formed by IL-12Rβ1 and IL-12Rβ2, mediates the type I immune responses of various types of lymphocytes. Polymorphisms in IL12RB2, the gene encoding IL-12Rβ2, were reported to be associated with several immune related diseases, such as Crohn's disease. Because the IL23R and IL12RB2 genes are located in close proximity on the genome, the reported associations might also be attributable to linked polymorphisms in IL23R, which were found to be associated with immune related diseases as well. To clarify the role of IL-12Rβ2 in immune diseases, we investigated the functional consequences of thirteen amino acid substitutions in IL-12Rβ2. We developed a model with retroviral expression of IL-12Rβ2 in B cell lines. With the use of this model the expression and function of the variants was compared within the same genetic background. Four of the IL-12Rβ2 variants, N271Y, R313G, A604V and L808R showed reduced IL-12 responses compared to the wild type variant. Two of these are relatively common in some populations and may be used in future association studies to reveal a role for IL-12 in infectious and/or immune related diseases. © 2013 Elsevier Ltd.

KW - Autoimmunity

KW - IL-12

KW - IL-12Rβ2

KW - IL12RB2

KW - Mutation

KW - Polymorphism

U2 - 10.1016/j.molimm.2013.07.002

DO - 10.1016/j.molimm.2013.07.002

M3 - Article

SN - 0161-5890

VL - 56

SP - 380

EP - 389

JO - Molecular immunology

JF - Molecular immunology

IS - 4

ER -

Differential expression and function of human IL-12Rβ2 polymorphic variants

Abstract

Keywords

UN SDGs

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