학술논문

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.
Document Type
Article
Source
Journal of Immunology. 6/15/2015, Vol. 194 Issue 12, p5609-5613. 5p.
Subject
*MULTIPLE sclerosis
*DEMYELINATION
*CENTRAL nervous system
*CELL differentiation
*LYMPHOID tissue
*T cells
Language
ISSN
0022-1767
Abstract
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/Wv) mice are less susceptible to EAE than are wild-type mice. However, male W/Wv mice exhibit exacerbated disease, a phenotype independent of mast cells and corresponding to a shift from a Th2- to a Thl7-dominated T cell response. We demonstrate a previously undescribed deficit in c-Kit+ type 2 innate lymphoid cells (ILC2s) in WAV' mice. ILC2s are also significantly reduced in EAEsusceptible 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. [ABSTRACT FROM AUTHOR]