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IL25 elicits a multipotent progenitor cell population that promotes T(H)2 cytokine responses.

TitleIL25 elicits a multipotent progenitor cell population that promotes T(H)2 cytokine responses.
Publication TypeJournal Article
Year of Publication2010
AuthorsSaenz SA, Siracusa MC, Perrigoue JG, Spencer SP, Urban JF, Tocker JE, Budelsky AL, Kleinschek MA, Kastelein RA, Kambayashi T, Bhandoola A, Artis D
JournalNature
Volume464
Issue7293
Pagination1362-6
Date Published2010 Apr 29
ISSN1476-4687
KeywordsAnimals, Antigens, Ly, Cell Differentiation, Cell Lineage, Granulocytes, Immunity, Innate, Immunity, Mucosal, Interleukins, Lymphoid Tissue, Macrophages, Membrane Proteins, Mice, Mice, Inbred Strains, Multipotent Stem Cells, Nippostrongylus, Proto-Oncogene Proteins c-kit, Strongylida Infections, Th2 Cells, Trichuriasis, Trichuris
Abstract

CD4(+) T helper 2 (T(H)2) cells secrete interleukin (IL)4, IL5 and IL13, and are required for immunity to gastrointestinal helminth infections. However, T(H)2 cells also promote chronic inflammation associated with asthma and allergic disorders. The non-haematopoietic-cell-derived cytokines thymic stromal lymphopoietin, IL33 and IL25 (also known as IL17E) have been implicated in inducing T(H)2 cell-dependent inflammation at mucosal sites, but how these cytokines influence innate immune responses remains poorly defined. Here we show that IL25, a member of the IL17 cytokine family, promotes the accumulation of a lineage-negative (Lin(-)) multipotent progenitor (MPP) cell population in the gut-associated lymphoid tissue that promotes T(H)2 cytokine responses. The IL25-elicited cell population, termed MPP(type2) cells, was defined by the expression of Sca-1 (also known as Ly6a) and intermediate expression of c-Kit (c-Kit(int)), and exhibited multipotent capacity, giving rise to cells of monocyte/macrophage and granulocyte lineages both in vitro and in vivo. Progeny of MPP(type2) cells were competent antigen presenting cells, and adoptive transfer of MPP(type2) cells could promote T(H)2 cytokine responses and confer protective immunity to helminth infection in normally susceptible Il25(-/-) mice. The ability of IL25 to induce the emergence of an MPP(type2) cell population identifies a link between the IL17 cytokine family and extramedullary haematopoiesis, and suggests a previously unrecognized innate immune pathway that promotes T(H)2 cytokine responses at mucosal sites.

DOI10.1038/nature08901
Alternate JournalNature
PubMed ID20200520
PubMed Central IDPMC2861732
Grant ListAI074878 / AI / NIAID NIH HHS / United States
AI083480 / AI / NIAID NIH HHS / United States
AI61570 / AI / NIAID NIH HHS / United States
F31GM082187 / GM / NIGMS NIH HHS / United States
P30 DK50306 / DK / NIDDK NIH HHS / United States
R01 AI061570 / AI / NIAID NIH HHS / United States
R01 AI061570-06 / AI / NIAID NIH HHS / United States
R01 AI074878 / AI / NIAID NIH HHS / United States
R01 AI074878-03 / AI / NIAID NIH HHS / United States
R01 AI095466 / AI / NIAID NIH HHS / United States
R01 AI102942 / AI / NIAID NIH HHS / United States
R21 AI083480 / AI / NIAID NIH HHS / United States
R21 AI083480-01 / AI / NIAID NIH HHS / United States
T32AI007532-08 / AI / NIAID NIH HHS / United States

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