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Genetic dissection of a major haplotype associated with autoimmune disease, FcγR2b and FcγR3 act additively

Genetic dissection of a major haplotype associated with autoimmune disease, FcγR2b and FcγR3 act additively
Genetic dissection of a major haplotype associated with autoimmune disease, FcγR2b and FcγR3 act additively
A haplotype with tightly linked Fc gamma receptor (FcγR) genes is known as a major locus controlling immune responses and autoimmune diseases, including arthritis. Here, we split a congenic fragment derived from the NOD mouse (Cia9) to study its effect on immune response and arthritis in mice. We found that arthritis susceptibility was indeed controlled by the FcγR gene cluster and a recombination between the FcγR2b and FcγR3 loci gave us the opportunity to separately study their impact. We identified the NOD‐derived FcγR2b and FcγR3 alleles as disease‐promoting for arthritis development without impact on antibody secretion. We further found that macrophage‐mediated phagocytosis was directly correlated to FcγR3 expression in the congenic mice. In conclusion, we positioned FcγR2b and FcγR3 alleles as disease regulatory and showed that their genetic polymorphisms independently and additively control innate immune cell activation and arthritis.
0014-2980
Vaartjes, Daniëlle
7ce8ac8c-fd2e-4436-98fe-f40e5b244b7b
Klaczkowska, Dorota
ce0a832d-5eed-4ca1-873f-0ab0ec1c63c4
Cragg, Mark
ec97f80e-f3c8-49b7-a960-20dff648b78c
Selva Nandakumar, Kutty
7145bd6d-3ac8-4323-8d6f-b41f9ead2cd5
Bäckdahl, Liselotte
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Holmdahl, Rikard
d8f359cd-41c4-459b-8479-c39020a23c04
Vaartjes, Daniëlle
7ce8ac8c-fd2e-4436-98fe-f40e5b244b7b
Klaczkowska, Dorota
ce0a832d-5eed-4ca1-873f-0ab0ec1c63c4
Cragg, Mark
ec97f80e-f3c8-49b7-a960-20dff648b78c
Selva Nandakumar, Kutty
7145bd6d-3ac8-4323-8d6f-b41f9ead2cd5
Bäckdahl, Liselotte
19ccf36b-4057-4bdb-843a-812c8e9b2b4f
Holmdahl, Rikard
d8f359cd-41c4-459b-8479-c39020a23c04

Vaartjes, Daniëlle, Klaczkowska, Dorota, Cragg, Mark, Selva Nandakumar, Kutty, Bäckdahl, Liselotte and Holmdahl, Rikard (2020) Genetic dissection of a major haplotype associated with autoimmune disease, FcγR2b and FcγR3 act additively. European Journal of Immunology. (doi:10.1002/eji.202048605).

Record type: Article

Abstract

A haplotype with tightly linked Fc gamma receptor (FcγR) genes is known as a major locus controlling immune responses and autoimmune diseases, including arthritis. Here, we split a congenic fragment derived from the NOD mouse (Cia9) to study its effect on immune response and arthritis in mice. We found that arthritis susceptibility was indeed controlled by the FcγR gene cluster and a recombination between the FcγR2b and FcγR3 loci gave us the opportunity to separately study their impact. We identified the NOD‐derived FcγR2b and FcγR3 alleles as disease‐promoting for arthritis development without impact on antibody secretion. We further found that macrophage‐mediated phagocytosis was directly correlated to FcγR3 expression in the congenic mice. In conclusion, we positioned FcγR2b and FcγR3 alleles as disease regulatory and showed that their genetic polymorphisms independently and additively control innate immune cell activation and arthritis.

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More information

Accepted/In Press date: 13 November 2020
e-pub ahead of print date: 26 November 2020

Identifiers

Local EPrints ID: 446815
URI: http://eprints.soton.ac.uk/id/eprint/446815
ISSN: 0014-2980
PURE UUID: 0f0c5686-b58e-4bc4-8e11-8c8008aafe93
ORCID for Mark Cragg: ORCID iD orcid.org/0000-0003-2077-089X

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Date deposited: 23 Feb 2021 17:32
Last modified: 26 Nov 2021 02:40

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Contributors

Author: Daniëlle Vaartjes
Author: Dorota Klaczkowska
Author: Mark Cragg ORCID iD
Author: Kutty Selva Nandakumar
Author: Liselotte Bäckdahl
Author: Rikard Holmdahl

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