Abstract |
Peptidyl arginine deiminase 4 (PAD4) is an enzyme that is involved in protein citrullination, and is a target for anti-citrullinated peptide antibodies ( ACPAs) in rheumatoid arthritis (RA). Genetic polymorphisms in the PADI4 gene encoding PAD4 are associated with RA susceptibility. We herein analyzed the roles of PADI4 in inflammatory arthritis using a glucose-6-phosphate isomerase (GPI)-induced arthritis (GIA) model in Padi4 knockout (KO) mice. Arthritis severity, serum anti-GPI antibody titers, and IL-6 concentrations were significantly reduced in Padi4 KO mice. The frequency of Th17 cells was decreased in GPI-immunized Padi4 KO mice, whereas WT and Padi4-deficient naïve CD4(+) T cells displayed the same efficiencies for Th17 cell differentiation in vitro. In addition, the numbers of myeloid lineage cells were reduced with the increased expression of pro-apoptotic genes in GPI-immunized Padi4 KO mice. Furthermore, the survival of Padi4-deficient neutrophils was impaired in vitro. Our results suggest that PADI4 exacerbates arthritis with diverse immunological modifications.
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Authors | Yu Seri, Hirofumi Shoda, Akari Suzuki, Isao Matsumoto, Takayuki Sumida, Keishi Fujio, Kazuhiko Yamamoto |
Journal | Scientific reports
(Sci Rep)
Vol. 5
Pg. 13041
(Aug 21 2015)
ISSN: 2045-2322 [Electronic] England |
PMID | 26293116
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies
- CD11b Antigen
- Interleukin-6
- Hydrolases
- PADI4 protein, human
- Protein-Arginine Deiminase Type 4
- Protein-Arginine Deiminases
- peptidylarginine deiminase 4, mouse
- Glucose-6-Phosphate Isomerase
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Topics |
- Animals
- Antibodies
(blood)
- Arthritis, Rheumatoid
(blood, chemically induced, enzymology, pathology)
- B-Lymphocytes
(metabolism)
- CD11b Antigen
(metabolism)
- Cell Differentiation
- Cell Proliferation
- Cell Survival
- Disease Models, Animal
- Glucose-6-Phosphate Isomerase
(immunology)
- Humans
- Hydrolases
(deficiency, metabolism)
- Immunization
- Interleukin-6
(blood)
- Lymphocyte Count
- Mice, Knockout
- Monocytes
(cytology)
- Neutrophils
(cytology)
- Protein-Arginine Deiminase Type 4
- Protein-Arginine Deiminases
- Severity of Illness Index
- Th17 Cells
(immunology)
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