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miR-146a Is Differentially Expressed by Myeloid Dendritic Cell Subsets and Desensitizes Cells to TLR2-Dependent Activation

Jurkin, Jennifer, Schichl, Yvonne M., Koeffel, Rene, Bauer, Thomas, Richter, Susanne, Konradi, Sabine, Gesslbauer, Bernhard, Strobl, Herbert·2010·The Journal of Immunology
DOI 10.4049/jimmunol.0903021
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Abstract

Langerhans cells (LCs) in epithelia and interstitial dendritic cells (intDCs) in adjacent connective tissues represent two closely related myeloid-derived DC subsets that exert specialized functions in the immune system and are of clinical relevance for cell therapy. Both subsets arise from monocyte-committed intermediates in response to tissue-associated microenvironmental signals; however, molecular mechanisms underlying myeloid DC subset specification and function remain poorly defined. Using microarray profiling, we identified microRNA (miRNA) miR-146a to be constitutively expressed at higher levels in human LCs compared with intDCs. Moreover, miR-146a levels were low in monocytes and nondetectable in neutrophil granulocytes. Interestingly, constitutive high miR-146a expression in LCs is induced by the transcription factor PU.1 in response to TGF-β1, a key microenvironmental signal for epidermal LC differentiation. We identified miR-146a as a regulator of monocyte and DC activation but not myeloid/DC subset differentiation. Ectopic miR-146a in monocytes and intDCs interfered with TLR2 downstream signaling and cytokine production, without affecting phenotypic DC maturation. Inversely, silencing of miR-146a in LCs enhanced TLR2-dependent NF-κB signaling. We therefore conclude that high constitutive miR-146a levels are induced by microenvironmental signals in the epidermis and might render LCs less susceptible to inappropriate activation by commensal bacterial TLR2 triggers at body surfaces.

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Metadata

Authors
Jurkin, J., Schichl, Y. M., Koeffel, R., Bauer, T., Richter, S., Konradi, S., Gesslbauer, B., & Strobl, H.
Affiliations
  • *Center of Physiology, Pathophysiology and Immunology, Institute of Immunology and
  • †Department of Vascular Biology and Thrombosis Research, Center of Biomolecular Medicine and Pharmacology, Medical University of Vienna, Vienna, Austria
Venue
The Journal of Immunology
Publisher
Oxford University Press (OUP)
Published
2010-05-01
Volume
184
Issue
9
Pages
4955-4965
ISSN
  • 0022-1767
  • 1550-6606
DOI
10.4049/jimmunol.0903021
Cited by
139
References
5
Language
en

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