Type 2 innate lymphoid cells control eosinophil homeostasis

By J. Nussbaum, S. V. Van Dyken, Jakob von Moltke, Laurence E. Cheng, Alexander Mohapatra, Ari B. Molofsky, E. Thornton, M. Krummel, A. Chawla, Hong-Erh Liang and 1 more. Nature, 2013

989 citations recorded by the source corpus.

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.

Subfields: Immunology, Surgery

View Paper: https://www.semanticscholar.org/paper/8714077d2c21ea37efa40228d6773470466a905a

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In Immunology

1. D. Artis
2. H. Spits
3. R. Locksley
4. A. Chawla
5. Andrew N. J. McKenzie
6. G. Eberl
7. A. Diefenbach
8. D. Umetsu

In Surgery

1. D. Artis
2. D. Umetsu
3. R. DeKruyff
4. Yajie Chang
5. Hye Young Kim
6. Sanhong Yu
7. Andrew N. J. McKenzie
8. H. Spits

Citations in the corpus

• Differentiation of type 1 ILCs from a common progenitor to all helper-like innate lymphoid cell lineages. (2014, positive): “ILC2s produce copious amounts of the ‘‘type 2’’ cytokines IL-5 and IL-13 (Moro et al., 2010; Neill et al., 2010) and play important roles in immunity to helminth infections (Neill et al., 2010) and in the pathogenesis of asthma and allergies (Nussbaum et al., 2013).”
• Innate Lymphoid Cells: a new paradigm in immunology (2015, background): “The production of IL-5 and IL-13 by ILC2s leads to the recruitment of eosinophils and the generation of alternatively activatedmacrophages (AAMs) that protect the organism from fat-induced ILC3mediated inflammatory pathology (74, 75).”
• Activated Type 2 Innate Lymphoid Cells regulate Beige Fat Biogenesis (2014, positive): “For these studies, we used heterozygous Red5 (Il5, R5) mice, which express tandem dimer red fluorescent protein (tdTomato) from the translation initiation site of the endogenous Il5 locus (Nussbaum et al., 2013), to monitor the fate and activation of ILC2s.”
• Innate Lymphoid Cells: 10 Years On. (2018, positive): “, 2017), and lung IL-5-producing ILC2s have been identified in collagen-rich regions close to the confluence of medium-sized blood vessels and airways (Nussbaum et al., 2013).”
• Innate lymphoid cells and asthma. (2014, positive): “In naive mice ILC2s represent the majority of IL-5–producing cells in the peripheral tissues, and ILC2s turn over more slowly compared with IL-5-producing CD4(1) T cells.(52) ILC2s thus maintain serum IL-5 levels in mice.”