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Published on: August 1, 2012
TNF-alpha regulates corneal Langerhans cell migration
1Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA.
Insights
Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) influence Langerhans cell (LC) migration in the cornea. TNF-alpha
Area of Science:
- Ophthalmology
- Immunology
- Cell Biology
Background:
- Langerhans cells (LCs) are crucial for immune responses on the ocular surface.
- LC migration into the cornea is vital for conditions like allograft rejection and herpetic keratitis.
- The precise molecular mechanisms governing ocular LC migration remain largely unknown.
Purpose of the Study:
- To investigate if TNF-alpha mediates corneal LC migration.
- To elucidate the interplay between IL-1 and TNF-alpha in regulating LC migratory capacity.
- To determine the roles of specific TNF receptor subunits (p55 and p75) in this process.
Main Methods:
- Utilized gene-targeted knockout mice lacking IL-1 receptor I (IL-1RI-/-), TNF receptor I (p55-/-), TNF receptor II (p75-/-), or both (p55-/-p75-/-).
- Induced LC migration via thermal cautery or intracorneal cytokine injection.
- Quantified LC migration using immunofluorescence assays.
Main Results:
- LC migration following cauterization or TNF-alpha injection was significantly reduced in p55-/- and p75-/- mice.
- Intracorneal IL-1alpha injection led to reduced LC migration in p55-/-, p75-/-, and p55-/-p75-/- mice within 72 hours.
- TNF-alpha injection in IL-1RI-/- mice resulted in normal corneal LC migration, indicating IL-1 receptor independence for TNF-alpha-induced migration.
Conclusions:
- IL-1-induced corneal LC migration is primarily mediated through TNF receptor (TNFR) signaling.
- TNF-alpha-induced LC migration in the cornea operates independently of IL-1 receptor I (IL-1RI) activity.
- Both p55 and p75 TNF receptor signaling pathways are essential for mediating LC migration in the cornea.
Abstract:
Langerhans cells (LC) belong to the dendritic cell family and mediate Ag presentation in the cornea and ocular surface. Under normal physiological conditions, the central cornea is devoid of LC. Centripetal migration of LC plays a critical role in promoting immunoinflammatory responses in the eye including allograft rejection and herpetic keratitis. The molecular mechanisms responsible for ocular LC migration are poorly understood. To examine whether TNF-alpha mediates corneal LC migration and to establish the interaction of IL-1 and TNF-alpha in regulating LC migratory capacity, we utilized gene-targeted knockout mice lacking IL-1 receptor I (IL-1RI-/-), TNF receptor I (p55-/-), TNF receptor II (p75-/-), or both (p55-/-p75-/-). LC migration was induced by thermal cautery or cytokine injection and enumerated by an immunofluorescence assay. Migration of LC after cauterization and TNF-alpha injection was significantly depressed in both p55-/- and p75-/- mice. Similarly, in the first 72 h after intracorneal injection of IL-1alpha, LC migration was reduced in p55-/-, p75-/-, and p55-/-p75-/- mice. In contrast, injection of TNF-alpha in IL-1RI-/- mice led to normal migration of corneal LC indistinguishable from wild-type controls. These results suggest that the IL-1 induction of corneal LC migration is largely mediated by TNFR function, whereas TNF-alpha induction of LC migration is independent of IL-1RI activity. Moreover, the data suggest that both p55 and p75 signaling pathways are important in mediating LC migration in the cornea.
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