The subunits of IL-12, originating from two distinct cells, can functionally synergize to protect against pathogen dissemination in vivo
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2021-10-12Journal
Cell ReportsPublisher
Elsevier Inc.Type
Article
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Cytokines 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.Rights/Terms
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.Keyword
CytokineCytokine signaling
Dendritic cell activation
Host Defense
IL-12
Leishmania
Pathogen trafficking
T cell differentiation
T cells
Tissue Immunity
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http://hdl.handle.net/10713/17008ae974a485f413a2113503eed53cd6c53
10.1016/j.celrep.2021.109816
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