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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

Shakya, Akhilesh Kumar; Kumar, Ashok; Klaczkowska, Dorota; Hultqvist, Malin LU ; Hagenow, Kristin; Holmdahl, Rikard LU and Kutty Selva, Nandakumar LU (2011) In American Journal of Pathology 179(5). p.2490-2500
Abstract
We established and characterized an arthritis mouse model using collagen type II (CH) 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-1 beta, 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... (More)
We established and characterized an arthritis mouse model using collagen type II (CH) 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-1 beta, 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 CH-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 V beta 12 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. (Am J Pathol 2011, 179:2490-2500; DOI: 10.1016/j.ajpath.2011.07.034) (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
American Journal of Pathology
volume
179
issue
5
pages
2490 - 2500
publisher
American Society for Investigative Pathology
external identifiers
  • wos:000298307600034
  • scopus:80054998857
ISSN
1525-2191
DOI
10.1016/j.ajpath.2011.07.034
language
English
LU publication?
yes
id
28ec65b7-b06d-41ff-8674-21ffece23499 (old id 2313135)
date added to LUP
2012-02-01 07:35:22
date last changed
2017-04-16 03:23:11
@article{28ec65b7-b06d-41ff-8674-21ffece23499,
  abstract     = {We established and characterized an arthritis mouse model using collagen type II (CH) 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-1 beta, 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 CH-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 V beta 12 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. (Am J Pathol 2011, 179:2490-2500; DOI: 10.1016/j.ajpath.2011.07.034)},
  author       = {Shakya, Akhilesh Kumar and Kumar, Ashok and Klaczkowska, Dorota and Hultqvist, Malin and Hagenow, Kristin and Holmdahl, Rikard and Kutty Selva, Nandakumar},
  issn         = {1525-2191},
  language     = {eng},
  number       = {5},
  pages        = {2490--2500},
  publisher    = {American Society for Investigative Pathology},
  series       = {American Journal of Pathology},
  title        = {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},
  url          = {http://dx.doi.org/10.1016/j.ajpath.2011.07.034},
  volume       = {179},
  year         = {2011},
}