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dc.contributor.authorGerber, Allison N
dc.contributor.authorAbdi, Kaveh
dc.contributor.authorSingh, Nevil J
dc.date.accessioned2021-10-28T18:38:04Z
dc.date.available2021-10-28T18:38:04Z
dc.date.issued2021-10-12en_US
dc.identifier.urihttp://hdl.handle.net/10713/17008
dc.description.abstractCytokines are typically single gene products, except for the heterodimeric interleukin (IL)-12 family. The two subunits (IL-12p40 and IL-12p35) of the prototype IL-12 are known to be simultaneously co-expressed in activated myeloid cells, which secrete the fully active heterodimer to promote interferon (IFN)γ production in innate and adaptive cells. We find that chimeric mice containing mixtures of cells that can only express either IL-12p40 or IL-12p35, but not both together, generate functional IL-12. This alternate two-cell pathway requires IL-12p40 from hematopoietic cells to extracellularly associate with IL-12p35 from radiation-resistant cells. The two-cell mechanism is sufficient to propel local T cell differentiation in sites distal to the initial infection and helps control systemic dissemination of a pathogen, although not parasite burden, at the site of infection. Broadly, this suggests that early secretion of IL-12p40 monomers by sentinel cells at the infection site may help prepare distal host tissues for potential pathogen arrival.en_US
dc.description.urihttps://doi.org/10.1016/j.celrep.2021.109816en_US
dc.language.isoenen_US
dc.publisherElsevier Inc.en_US
dc.relation.ispartofCell Reportsen_US
dc.rightsCopyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.en_US
dc.subjectCytokineen_US
dc.subjectCytokine signalingen_US
dc.subjectDendritic cell activationen_US
dc.subjectHost Defenseen_US
dc.subjectIL-12en_US
dc.subjectLeishmaniaen_US
dc.subjectPathogen traffickingen_US
dc.subjectT cell differentiationen_US
dc.subjectT cellsen_US
dc.subjectTissue Immunityen_US
dc.titleThe subunits of IL-12, originating from two distinct cells, can functionally synergize to protect against pathogen dissemination in vivoen_US
dc.typeArticleen_US
dc.identifier.doi10.1016/j.celrep.2021.109816
dc.identifier.pmid34644571
dc.source.volume37
dc.source.issue2
dc.source.beginpage109816
dc.source.endpage
dc.source.countryUnited States


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