Peptidylarginine Deiminase 2 in Murine Antiviral and Autoimmune Antibody Responses

The peptidylarginine deiminases (PADs) and the citrullinated proteins that they generate have key roles in innate immunity and rheumatoid arthritis, an inflammatory arthritis with antibodies that target citrullinated proteins. However, the importance of PADs, particularly PAD2, in the adaptive immun...

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Main Authors: Aisha M. Mergaert, Michael F. Denny, Brock Kingstad-Bakke, Mandar Bawadekar, S. Janna Bashar, Thomas F. Warner, Marulasiddappa Suresh, Miriam A. Shelef
Format: Article
Language:English
Published: Wiley 2022-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2022/5258221
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author Aisha M. Mergaert
Michael F. Denny
Brock Kingstad-Bakke
Mandar Bawadekar
S. Janna Bashar
Thomas F. Warner
Marulasiddappa Suresh
Miriam A. Shelef
author_facet Aisha M. Mergaert
Michael F. Denny
Brock Kingstad-Bakke
Mandar Bawadekar
S. Janna Bashar
Thomas F. Warner
Marulasiddappa Suresh
Miriam A. Shelef
author_sort Aisha M. Mergaert
collection DOAJ
description The peptidylarginine deiminases (PADs) and the citrullinated proteins that they generate have key roles in innate immunity and rheumatoid arthritis, an inflammatory arthritis with antibodies that target citrullinated proteins. However, the importance of PADs, particularly PAD2, in the adaptive immune response, both normal and pathogenic, is newly emerging. In this study, we evaluated a requirement for PAD2 in the antibody response in collagen-induced arthritis (CIA), a T and B cell-driven murine model of rheumatoid arthritis, and in the protective antibody response to murine influenza infection. Using PAD2-/- and PAD2+/+ mice on the DBA/1J background, we found that PAD2 is required for maximal anti-collagen antibody levels, but not collagen-specific plasma cell numbers, T cell activation or polarization, or arthritis severity in CIA. Also, we found that PAD2 is required not just for normal levels of persistent hemagglutination inhibiting antibodies but also for full protection from lethal influenza rechallenge. Together, these data provide evidence for a novel modest requirement for PAD2 in a normal antiviral antibody response and in an abnormal autoantibody response in inflammatory arthritis.
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spelling doaj-art-6fd59b6353344d72996e41b25de3b5fa2025-02-03T06:11:19ZengWileyJournal of Immunology Research2314-71562022-01-01202210.1155/2022/5258221Peptidylarginine Deiminase 2 in Murine Antiviral and Autoimmune Antibody ResponsesAisha M. Mergaert0Michael F. Denny1Brock Kingstad-Bakke2Mandar Bawadekar3S. Janna Bashar4Thomas F. Warner5Marulasiddappa Suresh6Miriam A. Shelef7Department of MedicineDepartment of MedicineDepartment of Pathobiological SciencesDepartment of MedicineDepartment of MedicineDepartment of Pathology and Laboratory MedicineDepartment of Pathobiological SciencesDepartment of MedicineThe peptidylarginine deiminases (PADs) and the citrullinated proteins that they generate have key roles in innate immunity and rheumatoid arthritis, an inflammatory arthritis with antibodies that target citrullinated proteins. However, the importance of PADs, particularly PAD2, in the adaptive immune response, both normal and pathogenic, is newly emerging. In this study, we evaluated a requirement for PAD2 in the antibody response in collagen-induced arthritis (CIA), a T and B cell-driven murine model of rheumatoid arthritis, and in the protective antibody response to murine influenza infection. Using PAD2-/- and PAD2+/+ mice on the DBA/1J background, we found that PAD2 is required for maximal anti-collagen antibody levels, but not collagen-specific plasma cell numbers, T cell activation or polarization, or arthritis severity in CIA. Also, we found that PAD2 is required not just for normal levels of persistent hemagglutination inhibiting antibodies but also for full protection from lethal influenza rechallenge. Together, these data provide evidence for a novel modest requirement for PAD2 in a normal antiviral antibody response and in an abnormal autoantibody response in inflammatory arthritis.http://dx.doi.org/10.1155/2022/5258221
spellingShingle Aisha M. Mergaert
Michael F. Denny
Brock Kingstad-Bakke
Mandar Bawadekar
S. Janna Bashar
Thomas F. Warner
Marulasiddappa Suresh
Miriam A. Shelef
Peptidylarginine Deiminase 2 in Murine Antiviral and Autoimmune Antibody Responses
Journal of Immunology Research
title Peptidylarginine Deiminase 2 in Murine Antiviral and Autoimmune Antibody Responses
title_full Peptidylarginine Deiminase 2 in Murine Antiviral and Autoimmune Antibody Responses
title_fullStr Peptidylarginine Deiminase 2 in Murine Antiviral and Autoimmune Antibody Responses
title_full_unstemmed Peptidylarginine Deiminase 2 in Murine Antiviral and Autoimmune Antibody Responses
title_short Peptidylarginine Deiminase 2 in Murine Antiviral and Autoimmune Antibody Responses
title_sort peptidylarginine deiminase 2 in murine antiviral and autoimmune antibody responses
url http://dx.doi.org/10.1155/2022/5258221
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