| Title |
Blockade of CD127 Exerts a Dichotomous Clinical Effect in Marmoset Experimental Autoimmune Encephalomyelitis
|
|---|---|
| Published in |
Journal of Neuroimmune Pharmacology, August 2015
|
| DOI | 10.1007/s11481-015-9629-6 |
| Pubmed ID | |
| Authors |
Jordon Dunham, Li-Fen Lee, Nikki van Driel, Jon D. Laman, Irene Ni, Wenwu Zhai, Guang-Huan Tu, John C. Lin, Jan Bauer, Bert A. ‘t Hart, Yolanda S. Kap |
| Abstract |
Non-human primate models of human disease have an important role in the translation of a new scientific finding in lower species into an effective treatment. In this study, we tested a new therapeutic antibody against the IL-7 receptor α chain (CD127), which in a C57BL/6 mouse model of experimental autoimmune encephalomyelitis (EAE) ameliorates disease, demonstrating an important pathogenic function of IL-7. We observed that while the treatment was effective in 100 % of the mice, it was only partially effective in the EAE model in common marmosets (Callithrix jacchus), a small-bodied Neotropical primate. EAE was induced in seven female marmoset twins and treatment with the anti-CD127 mAb or PBS as control was started 21 days after immunization followed by weekly intravenous administration. The anti-CD127 mAb caused functional blockade of IL-7 signaling through its receptor as shown by reduced phosphorylation of STAT5 in lymphocytes upon stimulation with IL-7. Group-wise analysis showed no significant effects on the clinical course and neuropathology. However, paired twin analysis revealed a delayed disease onset in three twins, which were high responders to the immunization. In addition, we observed markedly opposite effects of the antibody on pathological changes in the spinal cord in high versus low responder twins. In conclusion, promising clinical effect of CD127 blockade observed in a standard inbred/SPF mouse EAE model could only be partially replicated in an outbred/non-SPF non-human primate EAE model. Only in high responders to the immunization we found a positive response to the treatment. The mechanism underpinning this dichotomous response will be discussed. |
Mendeley readers
The data shown below were compiled from readership statistics for 13 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 13 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 2 | 15% |
| Student > Ph. D. Student | 2 | 15% |
| Other | 1 | 8% |
| Student > Bachelor | 1 | 8% |
| Student > Master | 1 | 8% |
| Other | 1 | 8% |
| Unknown | 5 | 38% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 2 | 15% |
| Pharmacology, Toxicology and Pharmaceutical Science | 1 | 8% |
| Agricultural and Biological Sciences | 1 | 8% |
| Psychology | 1 | 8% |
| Energy | 1 | 8% |
| Other | 0 | 0% |
| Unknown | 7 | 54% |
Attention Score in Context
This research output has an Altmetric Attention Score of 12. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 12 March 2024.
All research outputs
#2,944,987
of 24,217,893 outputs
Outputs from Journal of Neuroimmune Pharmacology
#76
of 583 outputs
Outputs of similar age
#37,469
of 268,696 outputs
Outputs of similar age from Journal of Neuroimmune Pharmacology
#1
of 10 outputs
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