title: CD4+ Group 1 Innate Lymphoid Cells (ILC) Form a Functionally Distinct ILC Subset That Is Increased in Systemic Sclerosis.
abstract: Innate lymphoid cells (ILC) are a heterogeneous group of cellular subsets that produce large amounts of T cell-associated cytokines in response to innate stimulation in the absence of Ag. In this study, we define distinct patterns of surface marker and cytokine expression among the ILC subsets that may further delineate their migration and function. Most notably, we found that the subset previously defined as group 1 ILC (ILC1) contains CD4(+) CD8(-), CD4(-) CD8(+), and CD4(-) CD8(-) populations. Although all ILC1 subsets shared characteristics with Th1 cells, CD4(+) ILC1 also demonstrated significant phenotypic and functional heterogeneity. We also show that the frequencies of CD4(+) ILC1 and NKp44(+) group 3 ILC, but not CD4(-) ILC1 or group 2 ILC, are increased in the peripheral blood of individuals with systemic sclerosis (SSc), a disease characterized by fibrotic and vascular pathology, as well as immune dysregulation. Furthermore, we demonstrate that CD4(+) and CD4(-) ILC1 are functionally divergent based on their IL-6Rα expression and that the frequency of IL-6Rα expression on ILC is altered in SSc. The distinct phenotypic and functional features of CD4(+) and CD4(-) ILC1 suggest that they may have differing roles in the pathogenesis of immune-mediated diseases, such as SSc.
authors.affiliation: Benaroya Research Institute at Virginia Mason, Seattle, WA.|University of Washington, Division of Allergy and Infectious Diseases, Seattle, WA.
authors.forename: Florence
authors.initials: F
authors.lastname: Roan
authors.affiliation: Benaroya Research Institute at Virginia Mason, Seattle, WA.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Stoklasek
authors.affiliation: Benaroya Research Institute at Virginia Mason, Seattle, WA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Whalen
authors.affiliation: University of Minnesota, Division of Rheumatology, Minneapolis, MN.
authors.forename: Jerry A
authors.initials: JA
authors.lastname: Molitor
authors.affiliation: University of California San Francisco, Diabetes Center, San Francisco, CA.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Bluestone
authors.affiliation: Benaroya Research Institute at Virginia Mason, Seattle, WA.
authors.forename: Jane H
authors.initials: JH
authors.lastname: Buckner
authors.affiliation: Benaroya Research Institute at Virginia Mason, Seattle, WA.
authors.forename: Steven F
authors.initials: SF
authors.lastname: Ziegler
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002469:Cell Separation; D005434:Flow Cytometry; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D012595:Scleroderma, Systemic / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
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