Selective control of SIRP-α–positive airway dendritic cell trafficking through CD47 is critical for the development of TH2-mediated allergic inflammation

Raymond, Marianne; Rubio, Manuel; Fortin, Genevieve; Shalaby, Karim H.; Hammad, Hamida; Lambrecht, Bart N.; Sarfati, Marika

doi:10.1016/j.jaci.2009.07.021

Cited by 77 publications

(94 citation statements)

References 44 publications

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“…Several investigators have shown that lung DC [9,43,54] or GM-CSF-cultured bonemarrow derived DC injected into the lung [55] are able to induce the typical Th2 response to inhaled allergen. Adoptive transfer studies showed that it is mainly the SIRPa 1 CD11b 1 lung DC that are efficient at Th2 priming, whereas Flt3L-cultured cDC are not [6,8]. The exact role of the CD11b À CD103 1 lung cDC in allergic sensitization or tolerance induction is a subject for further study.…”

Section: The Role Of Lung DC Subsets In Allergy and Asthmamentioning

confidence: 97%

“…Depletion of these DC at the time of lung allergen challenge reduces the salient features of asthma, such as airway eosinophilia, metaplasia of goblet cells and bronchial hyperreactivity [4,24]. The phenotype of these mice was restored by adoptive transfer of GM-CSF-cultured CD11b 1 DC, which most closely related to monocyte-derived inflammatory DC [6,59]. The function of DC during allergen challenge could be the local restimulation of effector function in lung resident lymphocytes, or alternatively could be the recruitment of these effector Th2 cells [60].…”

Section: The Role Of Lung DC Subsets In Allergy and Asthmamentioning

confidence: 99%

“…Immediately below, the lamina propria contains CD11b hi cDC [3][4][5] that express the SIRPa molecule (a ligand of CD47), and the CX3CR1 fractalkine receptor [6,7]. The conducting airways also contain pDC, best identified by additional staining for Siglec-H, or bone-marrow stromal antigen-2 (BST2) [1,2,8,9].…”

Section: Introducing Lung DC Heterogeneitymentioning

confidence: 99%

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Origin and functional specializations of DC subsets in the lung

2010

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Lung DC bridge innate and adaptive immunity, and depending on the context, induce Th1, Th2 or Th17 response, to optimally clear infections. Conversely, lung DC can also prevent overt and harmful immune responses to harmless inhaled antigens via induction of Treg cells or via induction of neutralizing mucosal IgA antibodies. Here, we propose that these functions are not the result of a single population of DC, and instead, subsets of DC perform specialized functions.

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Section: The Role Of Lung DC Subsets In Allergy and Asthmamentioning

confidence: 97%

Section: The Role Of Lung DC Subsets In Allergy and Asthmamentioning

confidence: 99%

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Origin and functional specializations of DC subsets in the lung

2010

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“…In addition, CD11b ϩ DCs in the lungs express both CD47 and SIRP␣, but CD103 ϩ DCs express only CD47. It was also demonstrated that CD47 helps CD11b ϩ DCs homing to draining lymph nodes during steady and inflammatory conditions (15). The populations of B220 ϩ B cells and CD8 ϩ T cells have been reported to remain unchanged in the spleens of SIRP␣ and CD47KO mice (16).…”

mentioning

confidence: 99%

“…However, a study reported that CD47-deficient (CD47KO) mice showed a defect in producing IgG antibodies to intravenous antigens (17). Another study using an allergic airway disease model demonstrated that antigen-specific antibody responses were lower in mucosal tissues from CD47KO mice (15). However, the role of CD47 in inducing specific antibodies in response to vaccination and protective immune responses against infectious viral disease remains largely unknown.…”

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confidence: 99%

CD47 Plays a Role as a Negative Regulator in Inducing Protective Immune Responses to Vaccination against Influenza Virus

Lee

et al. 2016

J Virol

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An integrin-associated protein CD47, which is a ligand for the inhibitory receptor signal regulatory protein ␣, is expressed on B and T cells, as well as on most innate immune cells. However, the roles of CD47 in the immune responses to viral infection or vaccination remain unknown. We investigated the role of CD47 in inducing humoral immune responses after intranasal infection with virus or immunization with influenza virus-like particles (VLPs). Virus infection or vaccination with VLPs containing hemagglutinin from A/PR8/34 influenza virus induced higher levels of antigen-specific IgG2c isotype dominant antibodies in CD47-deficient (CD47KO) mice than in wild-type (WT) mice. CD47KO mice with vaccination showed greater protective efficacy against lethal challenge, as evidenced by no loss in body weight and reduced lung viral titers compared to WT mice. In addition, inflammatory responses which include cytokine production, leukocyte infiltrates, and gamma interferon-producing CD4 ؉ T cells, as well as an anti-inflammatory cytokine (interleukin-10), were reduced in the lungs of vaccinated CD47KO mice after challenge with influenza virus. Analysis of lymphocytes indicated that GL7 ؉ germinal center B cells were induced at higher levels in the draining lymph nodes of CD47KO mice compared to those in WT mice. Notably, CD47KO mice exhibited significant increases in the numbers of antigen-specific memory B cells in spleens and plasma cells in bone marrow despite their lower levels of background IgG antibodies. These results suggest that CD47 plays a role as a negative regulator in inducing protective immune responses to influenza vaccination. I nfluenza viruses are common pathogens in the respiratory tract that are highly contagious and can cause pulmonary diseases. Seasonal influenza virus variants annually cause significant levels of morbidity and mortality, mostly in infants, the elderly, and sick people (1, 2). Vaccination is the most effective measure to prevent infections with a variety of pathogens, including influenza virus. Virus-like particles (VLPs) are able to effectively stimulate antigen-presenting cells (APCs), which in turn activate T and B cells (3-6). It has been demonstrated that immunization with influenza VLPs can induce protective humoral responses against seasonal and pandemic influenza virus infections (7-9). However, the mechanisms for evoking long-lasting immune responses are largely unknown.CD47 is a transmembrane protein, which is first identified as integrin ␣v␤3. CD47 that is expressed on hematopoietic and nonhematopoietic cells can interact with an inhibitory receptor signal regulatory protein ␣ (SIRP␣) (10). SIRP␣ is also expressed on dendritic cells (DCs) and macrophages, whereas SIRP␣ is barely expressed on B and T cells (11,12). It has been demonstrated that CD47/CD47 and CD47/SIRP␣ interactions are important for DC and neutrophil migration (13,14). In addition, CD11b ϩ DCs in the lungs express both CD47 and SIRP␣, but CD103 ϩ DCs express only CD47. It was also demonstrated t...

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Catching Our Breath: Updates on the Role of Dendritic Cell Subsets in Asthma

Lajiness

Cook‐Mills

2023

Advanced Biology

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Dendritic cells (DCs), as potent antigen presenting cells, are known to play a central role in the pathophysiology of asthma. The understanding of DC biology has evolved over the years to include multiple subsets of DCs with distinct functions in the initiation and maintenance of asthma. Furthermore, asthma is increasingly recognized as a heterogeneous disease with potentially diverse underlying mechanisms. The goal of this review is to summarize the role of DCs and the various subsets therein in the pathophysiology of asthma and highlight some of the crucial animal models shaping the field today. Potential future avenues of investigation to address existing gaps in knowledge are discussed.

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Selective control of SIRP-α–positive airway dendritic cell trafficking through CD47 is critical for the development of TH2-mediated allergic inflammation

Cited by 77 publications

References 44 publications

Origin and functional specializations of DC subsets in the lung

Origin and functional specializations of DC subsets in the lung

CD47 Plays a Role as a Negative Regulator in Inducing Protective Immune Responses to Vaccination against Influenza Virus

Catching Our Breath: Updates on the Role of Dendritic Cell Subsets in Asthma

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