Role of IL-18 induced Amphiregulin expression on virus induced ocular lesions
| Autor: | Ujjaldeep Jaggi, Siva Karthik Varanasi, Naveen K. Rajasagi, Barry T. Rouse |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
medicine.medical_treatment Immunology Amphiregulin T-Lymphocytes Regulatory p38 Mitogen-Activated Protein Kinases Article Pathogenesis Lesion Cornea 03 medical and health sciences Mice T-Lymphocyte Subsets Immunology and Allergy Medicine Animals Simplexvirus Gene knockout Mice Knockout Receptors Interleukin-18 business.industry Effector Interleukin-18 Herpes Simplex Interleukin-12 3. Good health Mice Inbred C57BL 030104 developmental biology Cytokine Cancer research Keratitis Herpetic Interleukin 18 Female Signal transduction medicine.symptom business Signal Transduction |
| Zdroj: | Mucosal immunology |
| ISSN: | 1935-3456 1933-0219 |
| Popis: | This report deals with the possible mechanism by which IL-18 can contribute to the control and resolution of inflammatory lesions in the cornea caused by herpes simplex virus infection. Our results demonstrate that the expression of the IL-18R by both regulatory T cells (Treg) and effector T cells was a pivotal event that influenced lesion pathogenesis. The engagement of IL-18R on Treg with its cytokine ligand resulted in Amphiregulin expression a molecule associated with tissue repair. In support of this scheme of events, lesion severity became more severe in animals unable to express the IL-18R because of gene knockout and was reduced in severity when IL-18 was overexpressed in the cornea. These changes in lesion severity correlated with the frequency and number of both Treg and Teff that expressed Amphiregulin. Additional experiments indicated that IL-12 and IL-18 acted synergistically to enhance Amphiregulin expression in Treg, an event partly dependent on P38 MAPK activity. Finally, sub-conjunctival administration of Amphiregulin resulted in resolution of both developing and developed lesions. Thus, overall our results imply that IL-18 may participate in controlling the severity of SK and contribute to tissue repair by converting both Treg and effector T cells into those that produce Amphiregulin. |
| Databáze: | OpenAIRE |
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