Semimature stage: a checkpoint in a dendritic cell maturation program that allows for functional reversion after signal-regulatory protein-alpha ligation and maturation signals.
CD47 on live cells actively engages signal-regulatory protein-alpha (SIRP-alpha) on phagocytes and delivers a negative signal that prevents their elimination. We evaluated the biological consequences of SIRP-alpha ligation on the dendritic cell (DC) response to maturation signals and the potential interplay with the IL-10/IL-10R inhibitory pathway. At first, CD47/SIRP-alpha allowed the generation of mature migratory DCs not producing IL-12, IFN-gamma-inducible protein-10, and CCL19. Rather, they secreted neutrophils attracting chemokine CXCL5 and IL-1beta, reflecting a partial block in functional DC maturation. Afterward, semimature DCs functionally regressed in an IL-10-independent fashion toward cells that retrieved the cardinal features of immature DCs: re-expression of CCR5, loss of DC-lysosome-associated membrane protein, high endocytosis, and impaired allostimulatory functions. The global gene expression profile of IL-10 and SIRP-alpha-ligated DC demonstrated two distinct molecular pathways. IL-10R and SIRP-alpha expression were reciprocally down-regulated by CD47 and IL-10, respectively. These results emphasize that the SIRP-alpha pathway might be part of the molecular machinery used by the DC to dampen or resolve an inflammatory response in an IL-10-independent manner.
Braun
Deborah
D
Immunoregulation Laboratory, Centre hospitalier de l'Université de Montréal Research Center, University of Montreal, 1560 Sherbrooke East, Montreal, Quebec, Canada.
Galibert
Laurent
L
Nakajima
Toshiharu
T
Saito
Hirohisa
H
Quang
Van Vu
VV
Rubio
Manuel
M
Sarfati
Marika
M
D000943:Antigens, Differentiation / Q000235:genetics / Q000502:physiology*; D051928:CD47 Antigen / Q000502:physiology; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000166:cytology* / Q000502:physiology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics; D011971:Receptors, Immunologic / Q000235:genetics / Q000502:physiology*; D053701:Receptors, Interleukin-10 / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction
D000943:Antigens, Differentiation; D051928:CD47 Antigen; D011971:Receptors, Immunologic; D053701:Receptors, Interleukin-10; C501920:SIRPA protein, human; D016753:Interleukin-10