Naslov
Endoplasmic reticulum-resident heat shock protein gp96, natural killer T cells and regulatory T cells as regulators of self-tissue damages induced by various types of injuries

Autori
Radošević-Stašić, Biserka ; Mrakovčić-Šutić, Ines ; Jakovac, Hrvoje ; Grebić, Damir ; Tomac, Jelena ; Rukavina, Daniel

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
American Journal of Reproductive Immunology / Beaman, Kenneth - Singapur : Markano Print Media PTe Ltd, 2007, 461-561

Skup
X International Congress of Reproductive Immunology

Mjesto i datum
Opatija, Hrvatska, 10.06.2007. - 14.06.2007

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
heat shock protein gp96; partial hepatectomy; stress; peptidoglycan monomer linked with zinc; liver; thymus

Sažetak
Problem: Various kinds of tissue disintegration lead in the endoplasmic reticulum (ER) to activation of adaptive pathways known as the ER stress response, which is directed to correction of unfolded proteins, to the activation of proteasome-dependent ER-associated degradation of the misfolded proteins and to activation of protein translation that modulate the polypeptide traffic into the ER. A crucial role in these events plays gp96, which acts not only as a molecular chaperone but also as an adjuvant, able to induce the specific immune response against some self and foreign antigens. Method of study: Since in the protection from the development of dangerous autoimmunity a special function might have self-reactive NKT cells and regulatory T cells (Treg) in this study we analysed the interplay between the gp96, NKT and Treg in conditions of: 1) normal growth, induced by partial hepatectomy, 2) in psychosocial stress without the tissue lesions and 3) after the treatment with bacterial peptidoglycan-monomer linked with zinc. Tissue expression of gp96 protein and mRNA was estimated in liver, thymus and spleen and the data were correlated with phenotype and cytotoxicity of hepatic and splenic mononuclear lymphatic cells (MNLC) against the syngeneic thymocytes, NK and LAK-sensitive targets. Results: All procedures induced fast cytoplasmic overexpression of gp96 staining in hepatocytes, followed by surface expression of gp96 on MNLC and upregulation of gp96 mRNA in the spleen and in the thymus. Simultaneously, in the liver accumulated CD3intermediate/NK1.1+/CD69+cells, as well as Treg cells, while hepatic (after initial suppression) and splenic MNLC became highly cytotoxic against syngeneic thymocytes and YAC-1 and P815. Conclusions: The data imply that during the disturbance of morphostasis gp96 may serve as a natural adjuvant for chaperoning antigenic self peptides into the immune surveillance pathways, resulting in activation of autoreactive NKT which in cooperation with Treg cells participate in reestablishment of self tolerance (Supported by grant 0621341-1337 from Croatian Ministry of Science).

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA