Your browser doesn't support javascript.
The persistence of interleukin-6 is regulated by a blood buffer system derived from dendritic cells.
Yousif, Ashraf S; Ronsard, Larance; Shah, Pankaj; Omatsu, Tatsushi; Sangesland, Maya; Bracamonte Moreno, Thalia; Lam, Evan C; Vrbanac, Vladimir D; Balazs, Alejandro B; Reinecker, Hans-Christian; Lingwood, Daniel.
  • Yousif AS; The Ragon Institute of Massachusetts General Hospital, The Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA.
  • Ronsard L; The Ragon Institute of Massachusetts General Hospital, The Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA.
  • Shah P; The Center for the Study of Inflammatory Bowel Disease, Center for Computational and Integrative Biology, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA.
  • Omatsu T; The Center for the Study of Inflammatory Bowel Disease, Center for Computational and Integrative Biology, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA.
  • Sangesland M; The Ragon Institute of Massachusetts General Hospital, The Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA.
  • Bracamonte Moreno T; The Ragon Institute of Massachusetts General Hospital, The Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA.
  • Lam EC; The Ragon Institute of Massachusetts General Hospital, The Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA.
  • Vrbanac VD; The Ragon Institute of Massachusetts General Hospital, The Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA.
  • Balazs AB; The Ragon Institute of Massachusetts General Hospital, The Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA.
  • Reinecker HC; The Center for the Study of Inflammatory Bowel Disease, Center for Computational and Integrative Biology, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA; The Center for the Genetics of Host Defense, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd.,
  • Lingwood D; The Ragon Institute of Massachusetts General Hospital, The Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA. Electronic address: dlingwood@mgh.harvard.edu.
Immunity ; 54(2): 235-246.e5, 2021 02 09.
Article in English | MEDLINE | ID: covidwho-988081
ABSTRACT
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.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Dendritic Cells / Interleukin-6 Limits: Animals Language: English Journal: Immunity Journal subject: Allergy and Immunology Year: 2021 Document Type: Article Affiliation country: J.immuni.2020.12.001

Similar

MEDLINE

...
LILACS

LIS


Full text: Available Collection: International databases Database: MEDLINE Main subject: Dendritic Cells / Interleukin-6 Limits: Animals Language: English Journal: Immunity Journal subject: Allergy and Immunology Year: 2021 Document Type: Article Affiliation country: J.immuni.2020.12.001