title: Type 2 innate lymphoid cells control eosinophil homeostasis.
abstract: Eosinophils are specialized myeloid cells associated with allergy and helminth infections. Blood eosinophils demonstrate circadian cycling, as described over 80 years ago, and are abundant in the healthy gastrointestinal tract. Although a cytokine, interleukin (IL)-5, and chemokines such as eotaxins mediate eosinophil development and survival, and tissue recruitment, respectively, the processes underlying the basal regulation of these signals remain unknown. Here we show that serum IL-5 levels are maintained by long-lived type 2 innate lymphoid cells (ILC2) resident in peripheral tissues. ILC2 cells secrete IL-5 constitutively and are induced to co-express IL-13 during type 2 inflammation, resulting in localized eotaxin production and eosinophil accumulation. In the small intestine where eosinophils and eotaxin are constitutive, ILC2 cells co-express IL-5 and IL-13; this co-expression is enhanced after caloric intake. The circadian synchronizer vasoactive intestinal peptide also stimulates ILC2 cells through the VPAC2 receptor to release IL-5, linking eosinophil levels with metabolic cycling. Tissue ILC2 cells regulate basal eosinophilopoiesis and tissue eosinophil accumulation through constitutive and stimulated cytokine expression, and this dissociated regulation can be tuned by nutrient intake and central circadian rhythms.
authors.affiliation: Department of Medicine, University of California San Francisco, San Francisco, California 94143-0795, USA.
authors.forename: Jesse C
authors.initials: JC
authors.lastname: Nussbaum
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Van Dyken
authors.forename: Jakob
authors.initials: J
authors.lastname: von Moltke
authors.forename: Laurence E
authors.initials: LE
authors.lastname: Cheng
authors.forename: Alexander
authors.initials: A
authors.lastname: Mohapatra
authors.forename: Ari B
authors.initials: AB
authors.lastname: Molofsky
authors.forename: Emily E
authors.initials: EE
authors.lastname: Thornton
authors.forename: Matthew F
authors.initials: MF
authors.lastname: Krummel
authors.forename: Ajay
authors.initials: A
authors.lastname: Chawla
authors.forename: Hong-Erh
authors.initials: HE
authors.lastname: Liang
authors.forename: Richard M
authors.initials: RM
authors.lastname: Locksley
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002940:Circadian Rhythm; D003094:Collagen / Q000378:metabolism; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism* / Q000469:parasitology; D005260:Female; D005786:Gene Expression Regulation; D006706:Homeostasis; D018793:Interleukin-13 / Q000235:genetics / Q000378:metabolism; D015848:Interleukin-5 / Q000097:blood / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000469:parasitology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009559:Nippostrongylus / Q000502:physiology; D017206:Strongylida Infections / Q000276:immunology
chemical_list: D018793:Interleukin-13; D015848:Interleukin-5; D003094:Collagen
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