BDNF and its receptors in human myasthenic thymus: implications for cell fate in thymic pathology.
Here we show that in myasthenic thymus several cell types, including thymic epithelial cells (TEC) and immune cells, were the source and the target of the neurotrophic factor brain-derived growth factor (BDNF). Interestingly, many actively proliferating medullary thymocytes expressed the receptor TrkB in vivo in involuted thymus, while this population was lost in hyperplastic or neoplastic thymuses. Furthermore, in hyperplastic thymuses the robust coordinated expression of BDNF in the germinal centers together with the receptor p75NTR on all proliferating B cells strongly suggests that this factor regulates germinal center reaction. Finally, all TEC dying of apoptosis expressed BDNF receptors, indicating that this neurotrophin is involved in TEC turnover. In thymomas both BDNF production and receptor expression in TEC were strongly hindered. This may represent an attempt of tumour escape from cell death.
Foundation IRCCS Neurological Institute Carlo Besta, Milan, Italy.
Angela
A
Berzi
C Korcan
CK
Ayata
Paola
P
Cavalcante
Chiara
C
Falcone
Elisabetta
E
Candiago
Teresio
T
Motta
Pia
P
Bernasconi
Reinhard
R
Hohlfeld
Renato
R
Mantegazza
Edgar
E
Meinl
Cinthia
C
Farina
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death; D002454:Cell Differentiation; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007633:Keratins / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000145:classification / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000473:pathology*; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000378:metabolism*; D013949:Thymus Extracts / Q000378:metabolism; D013950:Thymus Gland / Q000473:pathology*
D015703:Antigens, CD; D019208:Brain-Derived Neurotrophic Factor; D019394:Ki-67 Antigen; D017475:Receptors, Nerve Growth Factor; D013949:Thymus Extracts; C019277:brain-derived growth factor; D007633:Keratins; D053148:Caspase 3