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IL-25 simultaneously elicits distinct populations of innate lymphoid cells and multipotent progenitor type 2 (MPPtype2) cells.

TitleIL-25 simultaneously elicits distinct populations of innate lymphoid cells and multipotent progenitor type 2 (MPPtype2) cells.
Publication TypeJournal Article
Year of Publication2013
AuthorsSaenz SA, Siracusa MC, Monticelli LA, Ziegler CGK, Kim BS, Brestoff JR, Peterson LW, E Wherry J, Goldrath AW, Bhandoola A, Artis D
JournalJ Exp Med
Volume210
Issue9
Pagination1823-37
Date Published2013 Aug 26
ISSN1540-9538
KeywordsAnimals, Immunity, Innate, Inflammation, Inhibitor of Differentiation Protein 2, Interleukin-17, Interleukins, Lymphocytes, Mice, Mice, Inbred C57BL, Multipotent Stem Cells, Phenotype, Protein Binding, Receptors, Interleukin, Signal Transduction, Th2 Cells, Transcription, Genetic, Transcriptome
Abstract

The predominantly epithelial cell-derived cytokines IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) can promote CD4(+) Th2 cell-dependent immunity, inflammation, and tissue repair at barrier surfaces through the induction of multiple innate immune cell populations. IL-25 and IL-33 were previously shown to elicit four innate cell populations, named natural helper cells, nuocytes, innate type 2 helper cells, and multipotent progenitor type 2 (MPP(type2)) cells, now collectively termed group 2 innate lymphoid cells (ILC2). In contrast to other types of ILC2, MPP(type2) cells exhibit multipotent potential and do not express T1/ST2 or IL-7Rα, suggesting that MPP(type2) cells may be a distinct population. Here, we show that IL-33 elicits robust ILC2 responses, whereas IL-25 predominantly promotes MPP(type2) cell responses at multiple tissue sites with limited effects on ILC2 responses. MPP(type2) cells were distinguished from ILC2 by their differential developmental requirements for specific transcription factors, distinct genome-wide transcriptional profile, and functional potential. Furthermore, IL-25-induced MPP(type2) cells promoted Th2 cytokine-associated inflammation after depletion of ILC2. These findings indicate that IL-25 simultaneously elicits phenotypically and functionally distinct innate lymphoid- and nonlymphoid-associated cell populations and implicate IL-25-elicited MPP(type2) cells and extramedullary hematopoiesis in the promotion of Th2 cytokine responses at mucosal surfaces.

DOI10.1084/jem.20122332
Alternate JournalJ. Exp. Med.
PubMed ID23960191
PubMed Central IDPMC3754870
Grant List2-P30 CA016520 / CA / NCI NIH HHS / United States
AI061570 / AI / NIAID NIH HHS / United States
AI074878 / AI / NIAID NIH HHS / United States
AI083480 / AI / NIAID NIH HHS / United States
AI087990 / AI / NIAID NIH HHS / United States
AI095466 / AI / NIAID NIH HHS / United States
AI095608 / AI / NIAID NIH HHS / United States
AI097333 / AI / NIAID NIH HHS / United States
AI102942 / AI / NIAID NIH HHS / United States
F32-AI085828 / AI / NIAID NIH HHS / United States
KL2-RR024132 / RR / NCRR NIH HHS / United States
P30 AR057217 / AR / NIAMS NIH HHS / United States
P30-DK050306 / DK / NIDDK NIH HHS / United States
R01 AI095466 / AI / NIAID NIH HHS / United States
T32 AI007532 / AI / NIAID NIH HHS / United States
T32 AI060516 / AI / NIAID NIH HHS / United States
T32-AI007532 / AI / NIAID NIH HHS / United States
T32-AI060516 / AI / NIAID NIH HHS / United States
U01 AI095608 / AI / NIAID NIH HHS / United States
U01 AI095608 / AI / NIAID NIH HHS / United States

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