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RORγt inhibition selectively targets IL-17 producing iNKT and γδ-T cells enriched in Spondyloarthritis patients

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Abstract
Dysregulated IL-23/IL-17 responses have been linked to psoriatic arthritis and other forms of spondyloarthritides (SpA). ROR gamma t, the key Thelperl7 (Th17) cell transcriptional regulator, is also expressed by subsets of innate-like T cells, including invariant natural killer T (iNKT) and gamma delta-T cells, but their contribution to SpA is still unclear. Here we describe the presence of particular ROR gamma t(+)T-be(lo)PLZF(-) iNKT and gamma delta-hi T cell subsets in healthy peripheral blood. ROR gamma t(+) iNKT and gamma delta-hi T cells show IL-23 mediated Th17-like immune responses and were clearly enriched within inflamed joints of SpA patients where they act as major IL-17 secretors. SpA derived iNKT and gamma delta-T cells showed unique and Th17-skewed phenotype and gene expression profiles. Strikingly, ROR gamma t inhibition blocked gamma delta 17 and iNKT17 cell function while selectively sparing IL-22(+) subsets. Overall, our findings highlight a unique diversity of human ROR gamma t(+) T cells and underscore the potential of ROR gamma t antagonism to modulate aberrant type 17 responses.
Keywords
ARYL-HYDROCARBON RECEPTOR, INTESTINAL INFLAMMATION, T(H)17, DIFFERENTIATION, PLZF CONTROLS, DOUBLE-BLIND, PHENOTYPE, ARTHRITIS, IMMUNITY, PROGRAM, INTERLEUKIN-17

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Chicago
Venken, Koen, Peggy Jacques, Céline Mortier, Mark E. Labadia, Tine Decruy, Julie Coudenys, Kathleen Hoyt, et al. 2019. “RORγt Inhibition Selectively Targets IL-17 Producing iNKT and γδ-T Cells Enriched in Spondyloarthritis Patients.” Nature Communications 10.
APA
Venken, K., Jacques, P., Mortier, C., Labadia, M. E., Decruy, T., Coudenys, J., Hoyt, K., et al. (2019). RORγt inhibition selectively targets IL-17 producing iNKT and γδ-T cells enriched in Spondyloarthritis patients. NATURE COMMUNICATIONS, 10.
Vancouver
1.
Venken K, Jacques P, Mortier C, Labadia ME, Decruy T, Coudenys J, et al. RORγt inhibition selectively targets IL-17 producing iNKT and γδ-T cells enriched in Spondyloarthritis patients. NATURE COMMUNICATIONS. 2019;10.
MLA
Venken, Koen et al. “RORγt Inhibition Selectively Targets IL-17 Producing iNKT and γδ-T Cells Enriched in Spondyloarthritis Patients.” NATURE COMMUNICATIONS 10 (2019): n. pag. Print.
@article{8601543,
  abstract     = {Dysregulated IL-23/IL-17 responses have been linked to psoriatic arthritis and other forms of spondyloarthritides (SpA). ROR gamma t, the key Thelperl7 (Th17) cell transcriptional regulator, is also expressed by subsets of innate-like T cells, including invariant natural killer T (iNKT) and gamma delta-T cells, but their contribution to SpA is still unclear. Here we describe the presence of particular ROR gamma t(+)T-be(lo)PLZF(-) iNKT and gamma delta-hi T cell subsets in healthy peripheral blood. ROR gamma t(+) iNKT and gamma delta-hi T cells show IL-23 mediated Th17-like immune responses and were clearly enriched within inflamed joints of SpA patients where they act as major IL-17 secretors. SpA derived iNKT and gamma delta-T cells showed unique and Th17-skewed phenotype and gene expression profiles. Strikingly, ROR gamma t inhibition blocked gamma delta 17 and iNKT17 cell function while selectively sparing IL-22(+) subsets. Overall, our findings highlight a unique diversity of human ROR gamma t(+) T cells and underscore the potential of ROR gamma t antagonism to modulate aberrant type 17 responses.},
  articleno    = {9},
  author       = {Venken, Koen and Jacques, Peggy and Mortier, C{\'e}line and Labadia, Mark E. and Decruy, Tine and Coudenys, Julie and Hoyt, Kathleen and Wayne, Anita L. and Hughes, Robert and Turner, Michael and Van Gassen, Sofie and Martens, Liesbet and Smith, Dustin and Harcken, Christian and Wahle, Joseph and Wang, Chao-Ting and Verheugen, Eveline and Schryvers, Nadia and Varkas, Ga{\"e}lle and Cypers, Heleen and Wittoek, Ruth and Piette, Yves and Gyselbrecht, Lieve and Van Calenbergh, Serge and Van den Bosch, Filip and Saeys, Yvan and Nabozny, Gerald and Elewaut, Dirk},
  issn         = {2041-1723},
  journal      = {NATURE COMMUNICATIONS},
  language     = {eng},
  pages        = {15},
  title        = {ROR\ensuremath{\gamma}t inhibition selectively targets IL-17 producing iNKT and \ensuremath{\gamma}\ensuremath{\delta}-T cells enriched in Spondyloarthritis patients},
  url          = {http://dx.doi.org/10.1038/s41467-018-07911-6},
  volume       = {10},
  year         = {2019},
}

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