2019
DOI: 10.1172/jci.insight.124885
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Sex-dependent factors encoded in the immune compartment dictate relapsing or progressive phenotype in demyelinating disease

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Cited by 7 publications
(11 citation statements)
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“…In an elegant recent study, it was shown that when transferred to syngeneic SJL/J hosts, splenocytes from in vivo-primed male, MOG-specific, transgenic TCR 1640 mice induced progressive EAE while female cells transferred RR-EAE (Dhaeze et al, 2019). In contrast to our findings, however, male splenocytes in this model did not appear to transfer disease of increased maximal severity relative to female cells.…”
Section: Discussioncontrasting
confidence: 99%
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“…In an elegant recent study, it was shown that when transferred to syngeneic SJL/J hosts, splenocytes from in vivo-primed male, MOG-specific, transgenic TCR 1640 mice induced progressive EAE while female cells transferred RR-EAE (Dhaeze et al, 2019). In contrast to our findings, however, male splenocytes in this model did not appear to transfer disease of increased maximal severity relative to female cells.…”
Section: Discussioncontrasting
confidence: 99%
“…In contrast to our findings, however, male splenocytes in this model did not appear to transfer disease of increased maximal severity relative to female cells. A key difference between this study and our own was that before transfer, Dhaeze et al (2019) stimulated splenocytes with IL-12 as well as IL-23 to reactivate both Th1 and Th17 cells. By contrast, we specifically generated Th17 cells that were RORgt + before adoptive transfer, and male 1C6 Th17 generated under these conditions induced an accelerated disease course of greater severity than that invoked by male Th1.…”
Section: Discussionmentioning
confidence: 90%
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“…Allometric scaling of this dosage based on body surface area factor as per published guidelines ( 57 ) equates it to about 0.4 mg/kg in mouse. To investigate whether a comparable dosage of our anti-DICAM monoclonal antibody (clone 9E9) could similarly influence disease development, we administered 0.2 mg/kg anti-DICAM antibody or isotype control (10 intraperitoneal treatments of 400 ng each; injected every other day starting at day 4) in two preclinical mouse models of MS. For these experiments, we used the TCR1640 SJL/J passive EAE models, in which the adoptive transfer of reactivated splenocytes from TCR1640 mice into naïve SJL/J mice causes female and male mice to mostly develop relapsing-remitting and progressive diseases, respectively, similarly to human RRMS and PMS ( 58 , 59 ). We chose to administer the treatment in these two models prophylactically to maximize its potential impact, especially after having lowered its dosage by about 350-fold.…”
Section: Resultsmentioning
confidence: 99%
“…When splenocytes are isolated from presymptomatic TCR1640 mice, stimulated with anti-CD3 under mixed Th1/Th17 differentiation conditions, and transferred to SJL/J mice, the hosts show differences in disease pattern that are dictated by the sex of the transferred cells: recipients of stimulated male splenocytes develop progressive disease while recipients of female cells show RR disease (34). B.…”
Section: Future Perspectivesmentioning
confidence: 99%