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10.1016/j.immuni.2020.12.001

http://scihub22266oqcxt.onion/10.1016/j.immuni.2020.12.001
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33357409!7836640!33357409
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suck abstract from ncbi


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pmid33357409      Immunity 2021 ; 54 (2): 235-246.e5
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  • The persistence of interleukin-6 is regulated by a blood buffer system derived from dendritic cells #MMPMID33357409
  • Yousif AS; Ronsard L; Shah P; Omatsu T; Sangesland M; Bracamonte Moreno T; Lam EC; Vrbanac VD; Balazs AB; Reinecker HC; Lingwood D
  • Immunity 2021[Feb]; 54 (2): 235-246.e5 PMID33357409show ga
  • The interleukin-6 (IL-6) membrane receptor and its circulating soluble form, sIL-6R, can be targeted by antibody therapy to reduce deleterious immune signaling caused by chronic overexpression of the pro-inflammatory cytokine IL-6. This strategy may also hold promise for treating acute hyperinflammation, such as observed in coronavirus disease 2019 (COVID-19), highlighting a need to define regulators of IL-6 homeostasis. We found that conventional dendritic cells (cDCs), defined in mice via expression of the transcription factor Zbtb46, were a major source of circulating sIL-6R and, thus, systemically regulated IL-6 signaling. This was uncovered through identification of a cDC-dependent but T cell-independent modality that naturally adjuvants plasma cell differentiation and antibody responses to protein antigens. This pathway was then revealed as part of a broader biological buffer system in which cDC-derived sIL-6R set the in-solution persistence of IL-6. This control axis may further inform the development of therapeutic agents to modulate pro-inflammatory immune reactions.
  • |ADAM17 Protein[MESH]
  • |Animals[MESH]
  • |Cell Differentiation[MESH]
  • |Dendritic Cells/*immunology[MESH]
  • |Immunity, Humoral[MESH]
  • |Immunoglobulin M/immunology[MESH]
  • |Inflammation[MESH]
  • |Interferon Regulatory Factors/genetics/immunology[MESH]
  • |Interleukin-6/*blood/genetics/*immunology[MESH]
  • |Membrane Glycoproteins/immunology[MESH]
  • |Mice[MESH]
  • |Mice, Inbred C57BL[MESH]
  • |Mice, Transgenic[MESH]
  • |Plasma Cells/immunology[MESH]
  • |Receptors, Interleukin-6/blood/immunology[MESH]
  • |Signal Transduction/immunology[MESH]
  • |Toll-Like Receptor 4/immunology[MESH]


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