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 genesShow others and affiliations
2011 (English)In: American Journal of Pathology, ISSN 0002-9440, E-ISSN 1525-2191, Vol. 179, no 5, p. 2490-2500Article in journal (Refereed) Published
Abstract [en]
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-1beta, IFN-gamma, 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 Vbeta12 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.
Place, publisher, year, edition, pages
New York: Elsevier, 2011. Vol. 179, no 5, p. 2490-2500
National Category
Immunology in the medical area
Identifiers
URN: urn:nbn:se:hh:diva-48867DOI: 10.1016/j.ajpath.2011.07.034ISI: 000298307600034PubMedID: 21933654Scopus ID: 2-s2.0-80054998857OAI: oai:DiVA.org:hh-48867DiVA, id: diva2:1718805
Note
Funding text: Supported by Alex and Eva Wallstrom, Professor Nanna Svartz, Ake Wieberg, Anne Greta Holger Crafoord, KI (Fobi), Swedish Rheumatism Association, King Gustaf V:s 80-years and Swedish Research Council, VR-Link (2008-6007) and VR-project grant (2009-2338). A.K.S. acknowledges the senior research fellowship (SRF) from Council of Scientific and Industrial Research, India.
2022-12-132022-12-132023-02-20Bibliographically approved