TY - JOUR
T1 - TLR10 suppresses the activation and differentiation of monocytes with effects on DC-mediated adaptive immune responses
AU - Hess, Nicholas J.
AU - Felicelli, Christopher
AU - Grage, Jennifer
AU - Tapping, Richard I.
N1 - Funding Information:
This work was supported by Grant 1R01-AI097639 from the National Institute of Allergy and Infectious Diseases (NIAID) of the U.S. National Institutes of Health. The authors thank the Functional Genomics, DNA Services, and HPCBio groups at the University of Illinois Urbana-Champaign, Roy J. Carver Biotechnology Center, for their assistance in designing, performing, and analyzing the RNA-sequencing data.
Publisher Copyright:
© Society for Leukocyte Biology.
PY - 2017/5
Y1 - 2017/5
N2 - TLRs are important pattern-recognition receptors involved in the activation of innate immune responses against foreign pathogens. TLR10 is the only TLR family member without a known ligand, signaling pathway, or clear cellular function. Previous work has shown that TLR10 suppresses proinflammatory cytokine production in response to TLR agonists in a mixed human mononuclear cell population. We report that TLR10 is preferentially expressed on monocytes and suppresses proinflammatory cytokine production resulting from either TLR or CD40 stimulation. TLR10 engagement affects both the MAPK and Akt signaling pathways, leading to changes in the transcriptome of isolated human monocytes. Differentiation of monocytes into dendritic cells in the presence of an aTLR10 mAb reduced the expression of maturation markers and the induction of proinflammatory cytokines, again in response to either TLR or CD40 stimulation. Finally, in coculture experiments, TLR10 differentiated dendritic cells exhibited a decreased capacity to activate T cells as measured by IL-2 and IFN-g production. These data demonstrate that TLR10 is a novel regulator of innate immune responses and of the differentiation of primary human monocytes into effective dendritic cells.
AB - TLRs are important pattern-recognition receptors involved in the activation of innate immune responses against foreign pathogens. TLR10 is the only TLR family member without a known ligand, signaling pathway, or clear cellular function. Previous work has shown that TLR10 suppresses proinflammatory cytokine production in response to TLR agonists in a mixed human mononuclear cell population. We report that TLR10 is preferentially expressed on monocytes and suppresses proinflammatory cytokine production resulting from either TLR or CD40 stimulation. TLR10 engagement affects both the MAPK and Akt signaling pathways, leading to changes in the transcriptome of isolated human monocytes. Differentiation of monocytes into dendritic cells in the presence of an aTLR10 mAb reduced the expression of maturation markers and the induction of proinflammatory cytokines, again in response to either TLR or CD40 stimulation. Finally, in coculture experiments, TLR10 differentiated dendritic cells exhibited a decreased capacity to activate T cells as measured by IL-2 and IFN-g production. These data demonstrate that TLR10 is a novel regulator of innate immune responses and of the differentiation of primary human monocytes into effective dendritic cells.
KW - Cytokines
KW - Regulation
KW - TLR
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U2 - 10.1189/jlb.3A1116-492R
DO - 10.1189/jlb.3A1116-492R
M3 - Article
C2 - 28235773
AN - SCOPUS:85018450741
VL - 101
SP - 1245
EP - 1252
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
SN - 0741-5400
IS - 5
ER -