A mutation in Themis contributes to anaphylaxis severity following oral peanut challenge in CC027 mice.
J Allergy Clin Immunol
; 154(2): 387-397, 2024 Aug.
Article
in En
| MEDLINE
| ID: mdl-38670234
ABSTRACT
BACKGROUND:
The development of peanut allergy is due to a combination of genetic and environmental factors, although specific genes have proven difficult to identify. Previously, we reported that peanut-sensitized Collaborative Cross strain CC027/GeniUnc (CC027) mice develop anaphylaxis upon oral challenge to peanut, in contrast to C3H/HeJ (C3H) mice.OBJECTIVE:
This study aimed to determine the genetic basis of orally induced anaphylaxis to peanut in CC027 mice.METHODS:
A genetic mapping population between CC027 and C3H mice was designed to identify the genetic factors that drive oral anaphylaxis. A total of 356 CC027xC3H backcrossed mice were generated, sensitized to peanut, then challenged to peanut by oral gavage. Anaphylaxis and peanut-specific IgE were quantified for all mice. T-cell phenotyping was conducted on CC027 mice and 5 additional Collaborative Cross strains.RESULTS:
Anaphylaxis to peanut was absent in 77% of backcrossed mice, with 19% showing moderate anaphylaxis and 4% having severe anaphylaxis. There were 8 genetic loci associated with variation in response to peanut challenge-6 associated with anaphylaxis (temperature decrease) and 2 associated with peanut-specific IgE levels. There were 2 major loci that impacted multiple aspects of the severity of acute anaphylaxis, at which the CC027 allele was associated with worse outcome. At one of these loci, CC027 has a private genetic variant in the Themis gene. Consistent with described functions of Themis, we found that CC027 mice have more immature T cells with fewer CD8+, CD4+, and CD4+CD25+CD127- regulatory T cells.CONCLUSIONS:
Our results demonstrate a key role for Themis in the orally reactive CC027 mouse model of peanut allergy.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Arachis
/
Immunoglobulin E
/
Peanut Hypersensitivity
/
Anaphylaxis
/
Mice, Inbred C3H
Limits:
Animals
Language:
En
Journal:
J Allergy Clin Immunol
Year:
2024
Type:
Article