title: Vitamin A Controls the Presence of RORγ+ Innate Lymphoid Cells and Lymphoid Tissue in the Small Intestine.
abstract: Changes in diet and microbiota have determining effects on the function of the mucosal immune system. For example, the active metabolite of vitamin A, retinoic acid (RA), has been described to maintain homeostasis in the intestine by its influence on both lymphocytes and myeloid cells. Additionally, innate lymphoid cells (ILCs), important producers of cytokines necessary for intestinal homeostasis, are also influenced by vitamin A in the small intestines. In this study, we show a reduction of both NCR(-) and NCR(+) ILC3 subsets in the small intestine of mice raised on a vitamin A-deficient diet. Additionally, the percentages of IL-22-producing ILCs were reduced in the absence of dietary vitamin A. Conversely, mice receiving additional RA had a specific increase in the NCR(-) ILC3 subset, which contains the lymphoid tissue inducer cells. The dependence of lymphoid tissue inducer cells on vitamin A was furthermore illustrated by impaired development of enteric lymphoid tissues in vitamin A-deficient mice. These effects were a direct consequence of ILC-intrinsic RA signaling, because retinoic acid-related orphan receptor γt-Cre × RARα-DN mice had reduced numbers of NCR(-) and NCR(+) ILC3 subsets within the small intestine. However, lymphoid tissue inducer cells were not affected in these mice nor was the formation of enteric lymphoid tissue, demonstrating that the onset of RA signaling might take place before retinoic acid-related orphan receptor γt is expressed on lymphoid tissue inducer cells. Taken together, our data show an important role for vitamin A in controlling innate lymphoid cells and, consequently, postnatal formed lymphoid tissues within the small intestines.
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, 1081 BT Amsterdam, the Netherlands; and.
authors.forename: Gera
authors.initials: G
authors.lastname: Goverse
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, 1649-028 Lisbon, Portugal.
authors.forename: Carlos
authors.identifier: 0000-0002-7797-3797
authors.initials: C
authors.lastname: Labao-Almeida
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, 1649-028 Lisbon, Portugal.
authors.forename: Manuela
authors.identifier: 0000-0002-0075-2400
authors.initials: M
authors.lastname: Ferreira
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, 1081 BT Amsterdam, the Netherlands; and.
authors.forename: Rosalie
authors.initials: R
authors.lastname: Molenaar
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, 1081 BT Amsterdam, the Netherlands; and.
authors.forename: Sigrid
authors.identifier: 0000-0003-2606-1023
authors.initials: S
authors.lastname: Wahlen
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, 1081 BT Amsterdam, the Netherlands; and.
authors.forename: Tanja
authors.initials: T
authors.lastname: Konijn
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, 1081 BT Amsterdam, the Netherlands; and.
authors.forename: Jasper
authors.identifier: 0000-0003-2243-4857
authors.initials: J
authors.lastname: Koning
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, 1649-028 Lisbon, Portugal.
authors.forename: Henrique
authors.initials: H
authors.lastname: Veiga-Fernandes
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, 1081 BT Amsterdam, the Netherlands; and r.mebius@vumc.nl.
authors.forename: Reina E
authors.initials: RE
authors.lastname: Mebius
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000235:genetics / Q000276:immunology; D007113:Immunity, Innate; D007421:Intestine, Small / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology*; D008221:Lymphoid Tissue / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000032:analysis; D015398:Signal Transduction; D014212:Tretinoin / Q000378:metabolism; D014801:Vitamin A / Q000008:administration & dosage / Q000378:metabolism*; D014802:Vitamin A Deficiency / Q000276:immunology*
chemical_list: D000950:Antigens, Ly; D055627:Natural Cytotoxicity Triggering Receptor 1; C118384:Ncr1 protein, mouse; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D014801:Vitamin A; D014212:Tretinoin