title: Renegade homeostatic cytokine responses in T1D: drivers of regulatory/effector T cell imbalance.
abstract: Homeostatic cytokines contribute to the balance between regulatory and effector T cells (Tregs and Teffs respectively) and are necessary to maintain peripheral tolerance. These cytokines include IL-2 that supports Treg and IL-7 and IL-15 that drive Teff. In overt settings of lost tolerance (i.e. graft rejection), IL-2 Treg signatures are decreased while IL-7 and IL-15 Teff signatures are often enhanced. Similar cytokine profile imbalances also occur in some autoimmune diseases. In type 1 diabetes (T1D), there are underlying defects in the IL-2 pathway and Teff cytokine blockade can prevent and treat diabetes in NOD mice. In this review, we summarize evidence of IL-2, IL-7 and IL-15 genetic and cellular alterations in T1D patients. We then discuss how the combined effect of these cytokine profiles may together contribute to altered Treg/Teff ratios and functions in T1D. Implications for combination therapies and suggestions for integrated cytokine and Treg/Teff biomarker development are then proposed.
authors.affiliation: Translational Research Program, Benaroya Research Institute, Seattle, WA, USA.
authors.forename: Shipra
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Translational Research Program, Benaroya Research Institute, Seattle, WA, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Cerosaletti
authors.affiliation: Translational Research Program, Benaroya Research Institute, Seattle, WA, USA. Electronic address: along@benaroyaresearch.org.
authors.forename: S Alice
authors.initials: SA
authors.lastname: Long
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D016176:T-Lymphocyte Subsets / Q000502:physiology*
chemical_list: D016207:Cytokines
keywords: Biomarkers; IL-15; IL-2; IL-7; T cells; Type 1 diabetes