Chronic rejection triggers the development of an aggressive intragraft immune response through recapitulation of lymphoid organogenesis.
The unwarranted persistence of the immunoinflammatory process turns this critical component of the body's natural defenses into a destructive mechanism, which is involved in a wide range of diseases, including chronic rejection. Performing a comprehensive analysis of human kidney grafts explanted because of terminal chronic rejection, we observed that the inflammatory infiltrate becomes organized into an ectopic lymphoid tissue, which harbors the maturation of a local humoral immune response. Interestingly, intragraft humoral immune response appeared uncoupled from the systemic response because the repertoires of locally produced and circulating alloantibodies only minimally overlapped. The organization of the immune effectors within adult human inflamed tissues recapitulates the biological program recently identified in murine embryos during the ontogeny of secondary lymphoid organs. When this recapitulation was incomplete, intragraft B cell maturation was impeded, limiting the aggressiveness of the local humoral response. Identification of the molecular checkpoints critical for completion of the lymphoid neogenesis program should help develop innovative therapeutic strategies to fight chronic inflammation.
Institut National de la Santé et de la Recherche Médicale U872, Centre de Recherche des Cordeliers, France. olivier.thaunatpastu@free.fr
Olivier
O
Thaunat
Natacha
N
Patey
Giuseppina
G
Caligiuri
Chantal
C
Gautreau
Maria
M
Mamani-Matsuda
Yahia
Y
Mekki
Marie-Caroline
MC
Dieu-Nosjean
Gérard
G
Eberl
René
R
Ecochard
Jean-Baptiste
JB
Michel
Stéphanie
S
Graff-Dubois
Antonino
A
Nicoletti
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D002908:Chronic Disease; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D018858:Germinal Center / Q000276:immunology / Q000473:pathology; D006084:Graft Rejection / Q000196:embryology / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000196:embryology / Q000276:immunology / Q000473:pathology; D007672:Kidney Cortex / Q000196:embryology / Q000276:immunology / Q000473:pathology; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology; D008221:Lymphoid Tissue / Q000196:embryology* / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D038081:Organogenesis / Q000235:genetics / Q000276:immunology*; D012189:Retrospective Studies; D046509:Tissue Culture Techniques