PMID- 19748659
OWN - NLM
STAT- MEDLINE
DCOM- 20100112
LR  - 20171116
IS  - 1097-6825 (Electronic)
IS  - 0091-6749 (Linking)
VI  - 124
IP  - 6
DP  - 2009 Dec
TI  - Selective control of SIRP-alpha-positive airway dendritic cell trafficking 
      through CD47 is critical for the development of T(H)2-mediated allergic 
      inflammation.
PG  - 1333-42.e1
LID - 10.1016/j.jaci.2009.07.021 [doi]
AB  - BACKGROUND: Dendritic cells (DCs) are essential for the initiation and 
      maintenance of T(H)2 responses to inhaled antigen that lead to the establishment 
      of allergic diseases. Two subpopulations of nonplasmacytoid DCs (ie, 
      CD11b(low)CD103+ and CD11b(high)CD103(-)) are found in lung/airway tissues. Yet 
      the identification and migratory properties of the DC subset that contributes to 
      T(H)2-mediated responses remain to be clarified. CD47, a signal regulatory 
      protein (SIRP)-alpha partner, reportedly governed skin DC migration. OBJECTIVE: 
      We here thought to investigate the role of CD47/SIRP-alpha interactions in airway 
      DC trafficking and the development of allergic airway inflammation. METHODS: We 
      characterized the DC influx into lungs and mediastinal lymph nodes in CD47(-/-) 
      and CD47(+/+) BALB/c mice by using experimental models of allergic asthma. Mice 
      were systemically (intraperitoneal ovalbumin/alum) or locally (intratracheal 
      ovalbumin-loaded bone marrow-derived DCs) immunized and challenged by ovalbumin 
      aerosol. We also evaluated the consequences of SIRP-alpha-Fc fusion molecule 
      administration on the induction of airway disease in BALB/c mice. RESULTS: 
      SIRP-alpha selectively identified the CD11b(high)CD103(-) DC subset that 
      predominantly accumulated in mediastinal lymph nodes during airway inflammation. 
      However, CD103(-)SIRP-alpha+ DC trafficking, T(H)2 responses, and airway disease 
      were impaired in CD47(-/-) mice. Importantly, the adoptive transfer of CD103(-) 
      SIRP-alpha+CD47(+/+) but not CD47(-/-) DCs elicited a strong T(H)2 response in 
      CD47(-/-) mice. Finally, the administration of SIRP-alpha-Fc molecule protected 
      BALB/c mice from allergic airway inflammation. CONCLUSION: Lung 
      CD11b(high)CD103(-)SIRP-alpha+ DC migration is governed by self-CD47 expression, 
      and manipulation of the CD47/SIRP-alpha pathway suppresses CD103(-)SIRP-alpha(+) 
      DC-driven pathogenic T(H)2 responses and airway inflammation.
FAU - Raymond, Marianne
AU  - Raymond M
AD  - Immunoregulation Laboratory, Centre Hospitalier de l'Universite de Montreal 
      Research Center, Hopital Notre-Dame, Montreal, Quebec, Canada.
FAU - Rubio, Manuel
AU  - Rubio M
FAU - Fortin, Genevieve
AU  - Fortin G
FAU - Shalaby, Karim Hamdy
AU  - Shalaby KH
FAU - Hammad, Hamida
AU  - Hammad H
FAU - Lambrecht, Bart N
AU  - Lambrecht BN
FAU - Sarfati, Marika
AU  - Sarfati M
LA  - eng
GR  - MOP-53152/Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Allergy Clin Immunol
JT  - The Journal of allergy and clinical immunology
JID - 1275002
RN  - 0 (CD47 Antigen)
RN  - 0 (Cd47 protein, mouse)
RN  - 0 (Cytokines)
RN  - 0 (Ptpns1 protein, mouse)
RN  - 0 (Receptors, Immunologic)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 9006-59-1 (Ovalbumin)
SB  - IM
MH  - Adoptive Transfer
MH  - Animals
MH  - CD47 Antigen/genetics/*metabolism
MH  - Cell Movement/drug effects/immunology
MH  - Cytokines/drug effects/immunology/metabolism
MH  - Dendritic Cells/drug effects/*immunology/metabolism
MH  - Female
MH  - Hypersensitivity/*immunology/metabolism
MH  - Inflammation/*immunology/metabolism
MH  - Lung/drug effects/*immunology/pathology
MH  - Lymph Nodes/drug effects/pathology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Knockout
MH  - Ovalbumin/immunology
MH  - Receptors, Immunologic/*metabolism
MH  - Recombinant Fusion Proteins/pharmacology
MH  - Th2 Cells/drug effects/immunology/metabolism
EDAT- 2009/09/15 06:00
MHDA- 2010/01/13 06:00
CRDT- 2009/09/15 06:00
PHST- 2009/05/13 00:00 [received]
PHST- 2009/07/09 00:00 [revised]
PHST- 2009/07/09 00:00 [accepted]
PHST- 2009/09/15 06:00 [entrez]
PHST- 2009/09/15 06:00 [pubmed]
PHST- 2010/01/13 06:00 [medline]
AID - S0091-6749(09)01089-6 [pii]
AID - 10.1016/j.jaci.2009.07.021 [doi]
PST - ppublish
SO  - J Allergy Clin Immunol. 2009 Dec;124(6):1333-42.e1. doi: 
      10.1016/j.jaci.2009.07.021.