Interleukin-12 and -23 Control Plasticity of CD127(+) Group 1 and Group 3 Innate Lymphoid Cells in the Intestinal Lamina Propria.

6533b82afe1ef96bd128c37b

RESEARCH PRODUCT

Interleukin-12 and -23 Control Plasticity of CD127(+) Group 1 and Group 3 Innate Lymphoid Cells in the Intestinal Lamina Propria.

Christianne J. Buskens Mette D. Hazenberg Hergen Spits Bianca Blom J. Marius Munneke Kristine Germar Michael Kofoed-nielsen Jochem H. Bernink Andreas Diefenbach Willem A. Bemelman Esther C. De Jong Lisette Krabbendam Konrad Gronke Julien Villaudy

subject

Interleukin 2 Receptors Retinoic Acid Cellular differentiation CD14 Immunology Interleukin-1beta Retinoic acid Lipopolysaccharide Receptors chemical and pharmacologic phenomena Tretinoin Mice SCID Biology Interleukin-12 Subunit p35 Interleukin-7 Receptor alpha Subunit chemistry.chemical_compound Mice Intestinal mucosa Crohn Disease Mice Inbred NOD medicine Immunology and Allergy Animals Humans Retinoid X Receptor gamma Lymphocytes Intestinal Mucosa Interleukin-7 receptor Cells Cultured Mice Knockout Retinoic Acid Receptor alpha Innate lymphoid cell virus diseases hemic and immune systems Cell Differentiation Dendritic Cells Nuclear Receptor Subfamily 1 Group F Member 3 Molecular biology Killer Cells Natural Mice Inbred C57BL Infectious Diseases chemistry Lymphocyte Transfusion Immunology Interleukin 12 Interleukin-23 Subunit p19 Interleukin-2 medicine.drug

description

Human group 1 ILCs consist of at least three phenotypically distinct subsets, including NK cells, CD127(+) ILC1, and intraepithelial CD103(+) ILC1. In inflamed intestinal tissues from Crohn's disease patients, numbers of CD127(+) ILC1 increased at the cost of ILC3. Here we found that differentiation of ILC3 to CD127(+) ILC1 is reversible in vitro and in vivo. CD127(+) ILC1 differentiated to ILC3 in the presence of interleukin-2 (IL-2), IL-23, and IL-1β dependent on the transcription factor RORγt, and this process was enhanced in the presence of retinoic acid. Furthermore, we observed in resection specimen from Crohn's disease patients a higher proportion of CD14(+) dendritic cells (DC), which in vitro promoted polarization from ILC3 to CD127(+) ILC1. In contrast, CD14(-) DCs promoted differentiation from CD127(+) ILC1 toward ILC3. These observations suggest that environmental cues determine the composition, function, and phenotype of CD127(+) ILC1 and ILC3 in the gut.

year	journal	country	edition	language
2015-07-01	Immunity

10.1016/j.immuni.2015.06.019 https://pubmed.ncbi.nlm.nih.gov/26187413