Cutting edge: c-Kit signaling differentially regulates type 2 innate lymphoid cell accumulation and susceptibility to central nervous system demyelination in male and female SJL mice.

Authors: Russi, Abigail E  Walker-Caulfield, Margaret E  Ebel, Mark E  Brown, Melissa A 
Citation: Russi AE, etal., J Immunol. 2015 Jun 15;194(12):5609-13. doi: 10.4049/jimmunol.1500068. Epub 2015 May 13.
Pubmed: (View Article at PubMed) PMID:25972476
DOI: Full-text: DOI:10.4049/jimmunol.1500068

Multiple sclerosis preferentially affects women, and this sexual dimorphism is recapitulated in the SJL mouse model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). In this study, we demonstrate that signaling through c-Kit exerts distinct effects on EAE susceptibility in male and female SJL mice. Previous studies in females show that Kit mutant (W/W(v)) mice are less susceptible to EAE than are wild-type mice. However, male W/W(v) mice exhibit exacerbated disease, a phenotype independent of mast cells and corresponding to a shift from a Th2- to a Th17-dominated T cell response. We demonstrate a previously undescribed deficit in c-Kit(+) type 2 innate lymphoid cells (ILC2s) in W/W(v) mice. ILC2s are also significantly reduced in EAE-susceptible wild-type females, indicating that both c-Kit signals and undefined male-specific factors are required for ILC2 function. We propose that deficiencies in Th2-promoting ILC2s remove an attenuating influence on the encephalitogenic T cell response and therefore increases disease susceptibility.


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CRRD Object Information
CRRD ID: 12910744
Created: 2017-06-23
Species: All species
Last Modified: 2017-06-23
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.