Deutsch
 
Hilfe Datenschutzhinweis Impressum
  DetailsucheBrowse

Datensatz

 
 
DownloadE-Mail
  The Immunoregulator Soluble TACI Is Released by ADAM10 and Reflects B Cell Activation in Autoimmunity

Hoffmann, F. S., Kuhn, P.-H., Laurent, S. A., Hauck, S. M., Berer, K., Wendlinger, S. A., et al. (2015). The Immunoregulator Soluble TACI Is Released by ADAM10 and Reflects B Cell Activation in Autoimmunity. JOURNAL OF IMMUNOLOGY, 194(2), 542-552. doi:10.4049/jimmunol.1402070.

Item is

Externe Referenzen

einblenden:

Urheber

einblenden:
ausblenden:
 Urheber:
Hoffmann, Franziska S.1, Autor
Kuhn, Peer-Hendrik1, Autor
Laurent, Sarah A.1, Autor
Hauck, Stefanie M.1, Autor
Berer, Kerstin2, Autor           
Wendlinger, Simone A.1, Autor
Krumbholz, Markus1, Autor
Khademi, Mohsen1, Autor
Olsson, Tomas1, Autor
Dreyling, Martin1, Autor
Pfister, Hans-Walter1, Autor
Alexander, Tobias1, Autor
Hiepe, Falk1, Autor
Kuempfel, Tania1, Autor
Crawford, Howard C.1, Autor
Wekerle, Hartmut2, Autor           
Hohlfeld, Reinhard1, Autor
Lichtenthaler, Stefan F.1, Autor
Meinl, Edgar1, Autor
Affiliations:
1external, ou_persistent22              
2Emeritus Group: Neuroimmunology / Wekerle, MPI of Neurobiology, Max Planck Society, ou_1113547              

Inhalt

einblenden:
ausblenden:
Schlagwörter: COMMON VARIABLE IMMUNODEFICIENCY; SYSTEMIC-LUPUS-ERYTHEMATOSUS; AMYLOID PRECURSOR PROTEIN; MULTIPLE-SCLEROSIS; GAMMA-SECRETASE; PLASMA-CELLS; IN-VIVO; RECEPTOR; DISEASE; CLEAVAGE
 Zusammenfassung: BAFF and a proliferation-inducing ligand (APRIL), which control B cell homeostasis, are therapeutic targets in autoimmune diseases. TACI-Fc (atacicept), a soluble fusion protein containing the extracellular domain of the BAFF-APRIL receptor TACI, was applied in clinical trials. However, disease activity in multiple sclerosis unexpectedly increased, whereas in systemic lupus erythematosus, atacicept was beneficial. In this study, we show that an endogenous soluble TACI (sTACI) exists in vivo. TACI proteolysis involved shedding by a disintegrin and metalloproteinase 10 releasing sTACI from activated B cells. The membrane-bound stub was subsequently cleaved by gamma-secretase reducing ligand-independent signaling of the remaining C-terminal fragment. The shed ectodomain assembled ligand independently in a homotypic way. It functioned as a decoy receptor inhibiting BAFF-and APRIL-mediated B cell survival and NF-kappa B activation. We determined sTACI levels in autoimmune diseases with established hyperactivation of the BAFF-APRIL system. sTACI levels were elevated both in the cerebrospinal fluid of the brain-restricted autoimmune disease multiple sclerosis correlating with intrathecal IgG production, as well as in the serum of the systemic autoimmune disease systemic lupus erythematosus correlating with disease activity. Together, we show that TACI is sequentially processed by a disintegrin and metalloproteinase 10 and gamma-secretase. The released sTACI is an immunoregulator that shares decoy functions with atacicept. It reflects systemic and compartmentalized B cell accumulation and activation.

Details

einblenden:
ausblenden:
Sprache(n): eng - English
 Datum: 2015
 Publikationsstatus: Erschienen
 Seiten: 11
 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: Expertenbegutachtung
 Identifikatoren: ISI: 000347176700007
DOI: 10.4049/jimmunol.1402070
 Art des Abschluß: -

Veranstaltung

einblenden:

Entscheidung

einblenden:

Projektinformation

einblenden:

Quelle 1

einblenden:
ausblenden:
Titel: JOURNAL OF IMMUNOLOGY
Genre der Quelle: Zeitschrift
 Urheber:
Affiliations:
Ort, Verlag, Ausgabe: 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA : AMER ASSOC IMMUNOLOGISTS
Seiten: - Band / Heft: 194 (2) Artikelnummer: - Start- / Endseite: 542 - 552 Identifikator: ISSN: 0022-1767