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Tytuł pozycji:

VISTA Re-programs Macrophage Biology Through the Combined Regulation of Tolerance and Anti-inflammatory Pathways.

Tytuł:
VISTA Re-programs Macrophage Biology Through the Combined Regulation of Tolerance and Anti-inflammatory Pathways.
Autorzy:
ElTanbouly, Mohamed A.
Schaafsma, Evelien
Smits, Nicole C.
Shah, Parth
Cheng, Chao
Burns, Christopher
Blazar, Bruce R.
Noelle, Randolph J.
Mabaera, Rodwell
Temat:
SEPTIC shock
SUPPRESSOR cells
BIOLOGY
INTERLEUKIN-6
Źródło:
Frontiers in Immunology; 10/15/2020, Vol. 11, pN.PAG-N.PAG, 14p
Czasopismo naukowe
We present the novel finding that V-domain Ig suppressor of T cell activation (VISTA) negatively regulates innate inflammation through the transcriptional and epigenetic re-programming of macrophages. Representative of VISTA re-programming is the ability of VISTA agonistic antibodies to augment LPS tolerance and reduce septic shock lethality in mice. This anti-inflammatory effect of anti-VISTA was mimicked in vitro demonstrating that anti-VISTA treatment caused a significant reduction in LPS-induced IL-12p40, IL-6, CXCL2, and TNF; all hallmark pro-inflammatory mediators of endotoxin shock. Even under conditions that typically "break" LPS tolerance, VISTA agonists sustained a macrophage anti-inflammatory profile. Analysis of the proteomic and transcriptional changes imposed by anti-VISTA show that macrophage re-programming was mediated by a composite profile of mediators involved in both macrophage tolerance induction (IRG1, miR221, A20, IL-10) as well as transcription factors central to driving an anti-inflammatory profile (e.g., IRF5, IRF8, NFKB1). These findings underscore a novel and new activity of VISTA as a negative checkpoint regulator that induces both tolerance and anti-inflammatory programs in macrophages and controls the magnitude of innate inflammation in vivo. [ABSTRACT FROM AUTHOR]
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