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@ARTICLE{Guo:177877,
      author       = {C. Guo and D. Reuss and J. D. Coey and S. Sukumar and B.
                      Lang and J. McLauchlan and S. Boulant$^*$ and M. L. Stanifer
                      and C. G. G. Bamford},
      title        = {{C}onserved {I}nduction of {D}istinct {A}ntiviral
                      {S}ignalling {K}inetics by {P}rimate {I}nterferon {L}ambda 4
                      {P}roteins.},
      journal      = {Frontiers in immunology},
      volume       = {12},
      issn         = {1664-3224},
      address      = {Lausanne},
      publisher    = {Frontiers Media},
      reportid     = {DKFZ-2021-02902},
      pages        = {772588},
      year         = {2021},
      abstract     = {Interferon lambdas (IFNλ) (also known as type III IFNs)
                      are critical cytokines that combat infection predominantly
                      at barrier tissues, such as the lung, liver, and
                      gastrointestinal tract. Humans have four IFNλs (1-4), where
                      IFNλ1-3 show $~80\%-95\%$ homology, and IFNλ4 is the most
                      divergent displaying only $~30\%$ sequence identity.
                      Variants in IFNλ4 in humans are associated with the outcome
                      of infection, such as with hepatitis C virus. However, how
                      IFNλ4 variants impact cytokine signalling in other tissues
                      and how well this is conserved is largely unknown. In this
                      study, we address whether differences in antiviral
                      signalling exist between IFNλ4 variants in human hepatocyte
                      and intestinal cells, comparing them to IFNλ3. We
                      demonstrate that compared to IFNλ3, wild-type human IFNλ4
                      induces a signalling response with distinct magnitudes and
                      kinetics, which is modified by naturally occurring variants
                      P70S and K154E in both cell types. IFNλ4's distinct
                      antiviral response was more rapid yet transient compared to
                      IFNλ1 and 3. Additionally, divergent antiviral kinetics
                      were also observed using non-human primate IFNλs and cell
                      lines. Furthermore, an IFNλ4-like receptor-interacting
                      interface failed to alter IFNλ1's kinetics. Together, our
                      data provide further evidence that major functional
                      differences exist within the IFNλ gene family. These
                      results highlight the possible tissue specialisation of
                      IFNλs and encourage further investigation of the divergent,
                      non-redundant activities of IFNλ4 and other IFNλs.},
      keywords     = {IFNL4 (Other) / antiviral (Other) / interferon (Other) /
                      kinetics (Other) / lambda (Other) / signalling (Other)},
      cin          = {F140},
      ddc          = {610},
      cid          = {I:(DE-He78)F140-20160331},
      pnm          = {316 - Infektionen, Entzündung und Krebs (POF4-316)},
      pid          = {G:(DE-HGF)POF4-316},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:34868037},
      pmc          = {pmc:PMC8636442},
      doi          = {10.3389/fimmu.2021.772588},
      url          = {https://inrepo02.dkfz.de/record/177877},
}