Collagen type II and a thermo-responsive polymer of N-isopropylacrylamide induce arthritis independent of Toll-like receptors: a strong influence by major histocompatibility complex class II and Ncf1 genes.

Abstract

We established and characterized an arthritis mouse model using collagen type II (CII) and a thermo-responsive polymer, poly(N-isopropylacrylamide) (PNiPAAm). The new PNiPAAm adjuvant is TLR-independent, as all immunized TLR including MyD88-deficient mice developed an anti-CII response. Unlike other adjuvants, PNiPPAm did not skew the cytokine response (IL-1β, IFN-γ, IL-4, and IL-17), as there was no immune deviation towards any one type of immune spectrum after immunization with CII/PNiPPAm. Hence, using PNiPAAm, we studied the actual immune response to the self-protein, CII. We observed arthritis and autoimmunity development in several murine strains having different major histocompatibility complex (MHC) haplotypes after CII/PNiPAAm immunization but with a clear MHC association pattern. Interestingly, C57Bl/6 mice did not develop CII-induced arthritis, with PNiPAAm demonstrating absolute requirement for a classical adjuvant. Presence of a gene (Ncf1) mutation in the NADPH oxidation complex has a profound influence in arthritis and using PNiPAAm we could show that the high CIA severity in Ncf1 mutated mice is independent of any classical adjuvant. Macrophages, neutrophils, eosinophils, and osteoclasts but not mast cells dominated the inflamed joints. Furthermore, arthritis induction in the adjuvant-free, eosinophil-dependent Vβ12 DBA/1 mice could be shown to develop arthritis independent of eosinophils using CII/PNiPAAm. Thus, biocompatible and biodegradable PNiPAAm offers unique opportunities to study actual autoimmunity independent of TLR and a particular cytokine phenotype profile.

• Authors: Akhilesh Kumar Shakya, Ashok Kumar, Dorota Klaczkowska, Malin Hultqvist, Kristin Hagenow, Rikard Holmdahl, Kutty Selva Nandakumar
• Journal: The American journal of pathology (Am J Pathol) Vol. 179 Issue 5 Pg. 2490-500 (Nov 2011) ISSN: 1525-2191 [Electronic] United States
• PMID: 21933654 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Chemical References

• Acrylamides
• Acrylic Resins
• Adjuvants, Immunologic
• Antibodies
• Collagen Type II
• Cytokines
• Histocompatibility Antigens Class II
• Immunoglobulin G
• Polymers
• Toll-Like Receptors
• poly-N-isopropylacrylamide
• NADPH Oxidases
• neutrophil cytosolic factor 1

Topics

• Acrylamides (immunology)
• Acrylic Resins
• Adjuvants, Immunologic
• Animals
• Antibodies (metabolism)
• Antibody Formation
• Arthritis, Rheumatoid (genetics, immunology)
• Collagen Type II (adverse effects, immunology)
• Cytokines (metabolism)
• Histocompatibility Antigens Class II (genetics)
• Immunoglobulin G (metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Mutation (genetics, immunology)
• NADPH Oxidases (genetics)
• Polymers
• Toll-Like Receptors (immunology)