| First Author | Yousif AS | Year | 2021 |
| Journal | Immunity | Volume | 54 |
| Issue | 2 | Pages | 235-246.e5 |
| PubMed ID | 33357409 | Mgi Jnum | J:303987 |
| Mgi Id | MGI:6693876 | Doi | 10.1016/j.immuni.2020.12.001 |
| Citation | Yousif AS, et al. (2021) The persistence of interleukin-6 is regulated by a blood buffer system derived from dendritic cells. Immunity 54(2):235-246.e5 |
| abstractText | 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. |
