Publication Date:
2013-09-17
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3795960/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3795960/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nussbaum, Jesse C -- Van Dyken, Steven J -- von Moltke, Jakob -- Cheng, Laurence E -- Mohapatra, Alexander -- Molofsky, Ari B -- Thornton, Emily E -- Krummel, Matthew F -- Chawla, Ajay -- Liang, Hong-Erh -- Locksley, Richard M -- AI007334/AI/NIAID NIH HHS/ -- AI007641/AI/NIAID NIH HHS/ -- AI026918/AI/NIAID NIH HHS/ -- AI030663/AI/NIAID NIH HHS/ -- AI078869/AI/NIAID NIH HHS/ -- DK063720/DK/NIDDK NIH HHS/ -- DP1 AR064158/AR/NIAMS NIH HHS/ -- HL107202/HL/NHLBI NIH HHS/ -- P01 HL024136/HL/NHLBI NIH HHS/ -- P01 HL107202/HL/NHLBI NIH HHS/ -- P30 DK063720/DK/NIDDK NIH HHS/ -- R01 AI030663/AI/NIAID NIH HHS/ -- R37 AI026918/AI/NIAID NIH HHS/ -- T32 AI007641/AI/NIAID NIH HHS/ -- T32 GM007618/GM/NIGMS NIH HHS/ -- T32 HD044331/HD/NICHD NIH HHS/ -- U19 AI077439/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2013 Oct 10;502(7470):245-8. doi: 10.1038/nature12526. Epub 2013 Sep 15.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, University of California San Francisco, San Francisco, California 94143-0795, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24037376" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Cells, Cultured
;
Circadian Rhythm
;
Collagen/metabolism
;
Eosinophils/immunology/*metabolism/parasitology
;
Female
;
Gene Expression Regulation
;
*Homeostasis
;
Interleukin-13/genetics/metabolism
;
Interleukin-5/blood/genetics/metabolism
;
Lung/immunology/metabolism/parasitology
;
Lymphocytes/immunology/*metabolism/parasitology
;
Male
;
Mice
;
Mice, Inbred C57BL
;
Nippostrongylus/physiology
;
Strongylida Infections/immunology
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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