title: IL-25 simultaneously elicits distinct populations of innate lymphoid cells and multipotent progenitor type 2 (MPPtype2) cells.
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.
authors: Department of Microbiology, Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors: Steven A
authors: SA
authors: Saenz
authors: Mark C
authors: MC
authors: Siracusa
authors: Laurel A
authors: LA
authors: Monticelli
authors: Carly G K
authors: CG
authors: Ziegler
authors: Brian S
authors: BS
authors: Kim
authors: Jonathan R
authors: JR
authors: Brestoff
authors: Lance W
authors: LW
authors: Peterson
authors: E John
authors: EJ
authors: Wherry
authors: Ananda W
authors: AW
authors: Goldrath
authors: Avinash
authors: A
authors: Bhandoola
authors: David
authors: D
authors: Artis
mesh_terms: D000818:Animals; D007113:Immunity, Innate / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D051797:Inhibitor of Differentiation Protein 2 / Q000378:metabolism; D020381:Interleukin-17 / Q000494:pharmacology*; D000067596:Interleukin-33; D007378:Interleukins / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D010641:Phenotype; D011485:Protein Binding / Q000187:drug effects / Q000276:immunology; D018123:Receptors, Interleukin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014158:Transcription, Genetic / Q000187:drug effects; D059467:Transcriptome
chemical_list: C497452:Idb2 protein, mouse; C506535:Il33 protein, mouse; D051797:Inhibitor of Differentiation Protein 2; D020381:Interleukin-17; D000067596:Interleukin-33; D007378:Interleukins; D018123:Receptors, Interleukin
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