Age-related changes in expression and function of Toll-like receptors in human skin
| Autor: | Marion Prior, Stefan Hacker, Alice Schöppl, Nousheen Iram, Adelheid Elbe-Bürger, Christian Fiala, Michael Mildner, Peter Petzelbauer, Erwin Tschachler |
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| Rok vydání: | 2012 |
| Předmět: |
Adult
Keratinocytes Aging Adolescent Expression Human skin Biology Young Adult 03 medical and health sciences 0302 clinical medicine Toll-like receptor Immunity Humans CXCL10 Function Child Molecular Biology Research Articles Cells Cultured Skin 030304 developmental biology 0303 health sciences Innate immune system integumentary system Tumor Necrosis Factor-alpha Interleukin-8 Toll-Like Receptors Infant Dendritic Cells Dendritic cell Middle Aged Acquired immune system Immunity Innate 3. Good health Chemokine CXCL10 Poly I-C Langerhans Cells Skin Diseases Viral Immunology TLR3 Cytokines Tumor necrosis factor alpha Keratinocyte Human 030215 immunology Developmental Biology |
| Zdroj: | Development (Cambridge, England) |
| ISSN: | 1477-9129 0950-1991 |
| DOI: | 10.1242/dev.083477 |
| Popis: | Toll-like receptors (TLRs) initiate innate immune responses and direct subsequent adaptive immunity. They play a major role in cutaneous host defense against micro-organisms and in the pathophysiology of several inflammatory skin diseases. To understand the role of TLRs in the acquisition of immunological competence, we conducted a comprehensive study to evaluate TLR expression and function in the developing human skin before and after birth and compared it with adults. We found that prenatal skin already expresses the same spectrum of TLRs as adult skin. Strikingly, many TLRs were significantly higher expressed in prenatal (TLRs 1-5) and infant and child (TLRs 1 and 3) skin than in adult skin. Surprisingly, neither dendritic cell precursors in prenatal skin nor epidermal Langerhans cells and dermal dendritic cells in adult skin expressed TLRs 3 and 6, whereas the staining pattern and intensity of both TLRs in fetal basal keratinocytes was almost comparable to those of adults. Stimulation of primary human keratinocytes from fetal, neonatal and adult donors with selected TLR agonists revealed that the synthetic TLR3 ligand poly (I:C) specifically, mimicking viral double-stranded RNA, induced a significantly enhanced secretion of CXCL8/IL8, CXCL10/IP-10 and TNFα in fetal and neonatal keratinocytes compared with adult keratinocytes. This study demonstrates quantitative age-specific modifications in TLR expression and innate skin immune reactivity in response to TLR activation. Thus, antiviral innate immunity already in prenatal skin may contribute to protect the developing human body from viral infections in utero in a scenario where the adaptive immune system is not yet fully functional. |
| Databáze: | OpenAIRE |
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