title: 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.
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/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.
authors.affiliation: Department of Microbiology and Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611; and.
authors.forename: Abigail E
authors.identifier: http://orcid.org/0000-0003-4725-2574
authors.initials: AE
authors.lastname: Russi
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, MN 55905.
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Walker-Caulfield
authors.affiliation: Department of Microbiology and Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611; and.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Ebel
authors.affiliation: Department of Microbiology and Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611; and m-brown12@northwestern.edu.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Brown
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D003711:Demyelinating Diseases / Q000276:immunology* / Q000378:metabolism*; D004195:Disease Models, Animal; D018450:Disease Progression; D004198:Disease Susceptibility; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000378:metabolism; D005260:Female; D007113:Immunity, Innate; D016130:Immunophenotyping; D018836:Inflammation Mediators / Q000378:metabolism; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D008407:Mast Cells / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism*; D012737:Sex Factors; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D019009:Proto-Oncogene Proteins c-kit