| 1. |
|
|
| 2. |
|
|
| 3. |
- Bersellini Farinotti, Alex, et al.
(författare)
-
Cartilage-binding antibodies induce pain through immune complex-mediated activation of neurons
- 2019
-
Ingår i: Journal of Experimental Medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 216:8, s. 1904-1924
-
Tidskriftsartikel (refereegranskat)abstract
- Rheumatoid arthritis-associated joint pain is frequently observed independent of disease activity, suggesting unidentified pain mechanisms. We demonstrate that antibodies binding to cartilage, specific for collagen type II (CII) or cartilage oligomeric matrix protein (COMP), elicit mechanical hypersensitivity in mice, uncoupled from visual, histological and molecular indications of inflammation. Cartilage antibody-induced pain-like behavior does not depend on complement activation or joint inflammation, but instead on tissue antigen recognition and local immune complex (IC) formation. smFISH and IHC suggest that neuronal Fcgr1 and Fcgr2b mRNA are transported to peripheral ends of primary afferents. CII-ICs directly activate cultured WT but not FcRγ chain-deficient DRG neurons. In line with this observation, CII-IC does not induce mechanical hypersensitivity in FcRγ chain-deficient mice. Furthermore, injection of CII antibodies does not generate pain-like behavior in FcRγ chain-deficient mice or mice lacking activating FcγRs in neurons. In summary, this study defines functional coupling between autoantibodies and pain transmission that may facilitate the development of new disease-relevant pain therapeutics.
|
|
| 4. |
- Cao, D., et al.
(författare)
-
Pathogenic autoreactive B cells are not negatively selected toward matrix protein collagen II
- 2011
-
Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 187:9, s. 4451-4458
-
Tidskriftsartikel (refereegranskat)abstract
- We have addressed the importance of B cell tolerance to collagen type II, a matrix protein, which is a target in rheumatoid arthritis (RA) and its mouse models. We generated a germline-encoded anti-collagen type II (CII) IgH replacement anti-C1 B cell mouse strain (ACB) to investigate how B cell tolerance to CII, a matrix protein, is subverted and to further understand pathogenesis of RA. Phenotypic analysis revealed that CII-specific B cells were surprisingly neither deleted nor anergized. Instead, they were readily detected in all lymphoid organs. Spontaneously produced autoantibodies could bind directly to cartilage surface without detectable pathology. However, exaggerated arthritis was seen after injection of anti-CII Abs specific for other epitopes. In addition, Abs from CII-specific hybridomas generated from ACB mice induced arthritis. Interestingly, IgH/L chain sequence data in B cell hybridomas revealed a lack of somatic mutations in autoreactive B cells. The ACB model provides the first possibility, to our knowledge, to study B cell tolerance to a matrix protein, and the observations made in the study could not be predicted from previous models. B cell-reactive epitopes on CII are largely shared between human RA and rodent CII-induced arthritis; this study, therefore, has important implications for further understanding of pathological processes in autoimmune diseases like RA.
|
|
| 5. |
|
|
| 6. |
- Perret, E., et al.
(författare)
-
Structural, magnetic and electronic properties of pulsed-laser-deposition grown SrFeO3-delta thin films and SrFeO3-delta/La2/3Ca1/3MnO3 multilayers
- 2017
-
Ingår i: Journal of Physics. - 0953-8984 .- 1361-648X. ; 29:49
-
Tidskriftsartikel (refereegranskat)abstract
- We studied the structural, magnetic and electronic properties of SrFeO3-delta (SFO) thin films and SrFeO3-delta/La2/3Ca1/3MnO3 (LCMO) superlattices that have been grown with pulsed laser deposition (PLD) on La0.3Sr0.7Al0.65Ta0.35O3 (LSAT) substrates. X-ray reflectometry and scanning transmission electron microscopy (STEM) confirm the high structural quality of the films and flat and atomically sharp interfaces of the superlattices. The STEM data also reveal a difference in the interfacial layer stacking with a SrO layer at the LCMO/SFO and a LaO layer at the SFO/LCMO interfaces along the PLD growth direction. The x-ray diffraction (XRD) data suggest that the as grown SFO films and SFO/LCMO superlattices have an oxygen-deficient SrFeO3-delta structure with I4/mmm space group symmetry (delta <= 0.2). Subsequent ozone annealed SFO films are consistent with an almost oxygen stoichiometric structure (delta approximate to 0). The electronic and magnetic properties of these SFO films are similar to the ones of corresponding single crystals. In particular, the as grown SrFeO3-delta films are insulating whereas the ozone annealed films are metallic. The magneto-resistance effects of the as grown SFO films have a similar magnitude as in the single crystals, but extend over a much wider temperature range. Last but not least, for the SFO/LCMO superlattices we observe a rather large exchange bias effect that varies as a function of the cooling field.
|
|
| 7. |
|
|
