Cytosolic PLA2 is required for CTL-mediated immunopathology of celiac disease via NKG2D and IL-15.
J Exp Med
; 206(3): 707-19, 2009 Mar 16.
Article
en En
| MEDLINE
| ID: mdl-19237603
ABSTRACT
IL-15 and NKG2D promote autoimmunity and celiac disease by arming cytotoxic T lymphocytes (CTLs) to cause tissue destruction. However, the downstream signaling events underlying these functional properties remain unclear. Here, we identify cytosolic phospholipase A(2) (cPLA(2)) as a central molecule in NKG2D-mediated cytolysis in CTLs. Furthermore, we report that NKG2D induces, upon recognition of MIC(+) target cells, the release of arachidonic acid (AA) by CTLs to promote tissue inflammation in association with target killing. Interestingly, IL-15, which licenses NKG2D-mediated lymphokine killer activity in CTLs, cooperates with NKG2D to induce cPLA(2) activation and AA release. Finally, cPLA(2) activation in intraepithelial CTLs of celiac patients provides an in vivo pathophysiological dimension to cPLA(2) activation in CTLs. These results reveal an unrecognized link between NKG2D and tissue inflammation, which may underlie the emerging role of NKG2D in various immunopathological conditions and define new therapeutic targets.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Linfocitos T Citotóxicos
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Enfermedad Celíaca
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Interleucina-15
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Fosfolipasas A2 Citosólicas
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Subfamilia K de Receptores Similares a Lectina de Células NK
Límite:
Humans
Idioma:
En
Revista:
J Exp Med
Año:
2009
Tipo del documento:
Article
País de afiliación:
Estados Unidos