VISTA is an activating receptor in human monocytes
Spotlight (1) Rogers BM (2) Smith L (3) Dezso Z (4) Shi X (5) DiGiammarino E (6) Nguyen D (7) Sethuraman S (8) Zheng P (9) Choi D (10) Zhang D (11) Nguyen A (12) McGuire K (13) Liu W (14) Chung N (15) Chao DT (16) Ye S (17) Starbeck-Miller GR
Using two novel VISTA-specific antibodies, Rogers et al. showed high levels of VISTA on primary human blood monocytes. In an Fc-dependent manner, the antibodies were agonistic, leading to enhanced expression of mediators of antigen presentation, leukocyte migration, cell adhesion, DC differentiation, and cytokine signaling. Monocytes also specifically bound a pentameric construction of VISTA’s extracellular domain, and the heparan sulfate proteoglycan (HSPG) Syndecan-2 was identified as the VISTA binding partner. HSPGs can also bind certain chemokines, suggesting the possibility of cis and trans immune regulatory networks in monocytes.
Contributed by Paula Hochman
(1) Rogers BM (2) Smith L (3) Dezso Z (4) Shi X (5) DiGiammarino E (6) Nguyen D (7) Sethuraman S (8) Zheng P (9) Choi D (10) Zhang D (11) Nguyen A (12) McGuire K (13) Liu W (14) Chung N (15) Chao DT (16) Ye S (17) Starbeck-Miller GR
Using two novel VISTA-specific antibodies, Rogers et al. showed high levels of VISTA on primary human blood monocytes. In an Fc-dependent manner, the antibodies were agonistic, leading to enhanced expression of mediators of antigen presentation, leukocyte migration, cell adhesion, DC differentiation, and cytokine signaling. Monocytes also specifically bound a pentameric construction of VISTA’s extracellular domain, and the heparan sulfate proteoglycan (HSPG) Syndecan-2 was identified as the VISTA binding partner. HSPGs can also bind certain chemokines, suggesting the possibility of cis and trans immune regulatory networks in monocytes.
Contributed by Paula Hochman
ABSTRACT: As indicated by its name, V-domain Ig suppressor of T cell activation (VISTA) is thought to serve primarily as an inhibitory protein that limits immune responses. VISTA antibodies can dampen the effects of several concomitantly elicited activation signals, including TCR and TLR activation, but it is currently unclear if VISTA agonism could singly affect immune cell biology. In this study, we discovered two novel VISTA antibodies and characterized their effects on human peripheral blood mononuclear cells by scRNA/CITE-seq. Both antibodies appeared to agonize VISTA in an Fc-functional manner to elicit transcriptional and functional changes in monocytes consistent with activation. We also used pentameric VISTA to identify Syndecan-2 and several heparan sulfate proteoglycan synthesis genes as novel regulators of VISTA interactions with monocytic cells, adding further evidence of bidirectional signaling. Together, our study highlights several novel aspects of VISTA biology that have yet to be uncovered in myeloid cells and serves as a foundation for future research.
Author Info: (1) AbbVie Biotherapeutics Inc., Redwood City, CA. (2) AbbVie Inc., North Chicago, IL. (3) AbbVie Biotherapeutics Inc., Redwood City, CA. (4) AbbVie Biotherapeutics Inc., Redwood C
Author Info: (1) AbbVie Biotherapeutics Inc., Redwood City, CA. (2) AbbVie Inc., North Chicago, IL. (3) AbbVie Biotherapeutics Inc., Redwood City, CA. (4) AbbVie Biotherapeutics Inc., Redwood City, CA. (5) AbbVie Inc., North Chicago, IL. (6) AbbVie Biotherapeutics Inc., Redwood City, CA. (7) AbbVie Inc., North Chicago, IL. (8) AbbVie Biotherapeutics Inc., Redwood City, CA. (9) AbbVie Biotherapeutics Inc., Redwood City, CA. (10) AbbVie Biotherapeutics Inc., Redwood City, CA. (11) AbbVie Biotherapeutics Inc., Redwood City, CA. (12) AbbVie Inc., North Chicago, IL. (13) AbbVie Biotherapeutics Inc., Redwood City, CA. (14) AbbVie Biotherapeutics Inc., Redwood City, CA. (15) AbbVie Biotherapeutics Inc., Redwood City, CA. (16) AbbVie Biotherapeutics Inc., Redwood City, CA. (17) AbbVie Biotherapeutics Inc., Redwood City, CA.
Citation: J Exp Med 2021 Aug 2 218: Epub06/09/2021