Fc Receptors in Mucosal Immunology

Egmond, Marjolein van; Bakema, Jantine E.; Woof, Jenny M.

doi:10.1016/b978-0-12-415847-4.00020-3

Cited by 7 publications

(16 citation statements)

References 231 publications

(265 reference statements)

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“…FcαRI is a transmembrane receptor and a member of the Fc receptor immunoglobulin (Ig) superfamily, which also includes Fc receptors for IgG (FcγR) and IgE (FcεRI) . However, the FcαRI gene is located on chromosome 19 (at 19q13.4) and lies within the so‐called leukocyte receptor cluster (LRC) , whereas genes encoding FcγR and FcεRI map on chromosome 1 (at 1q21‐23) .…”

Section: Expression and Structure Of Fcαrimentioning

confidence: 99%

“…In the absence of this compensatory mechanism, patients can develop severe diseases . Perhaps the most convincing evidence backing the significance of IgA in protective immunity is the fact that bacterial evolution resulted in the development of anti‐IgA or anti‐FcαRI bacterial proteins that obstruct IgA–FcαRI interactions . This likely represents an important evasion strategy for the pathogens to escape IgA‐mediated elimination by FcαRI‐expressing phagocytes.…”

Section: Introductionmentioning

confidence: 99%

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The era of the immunoglobulin A Fc receptor FcαRI; its function and potential as target in disease

Aleyd

Heineke

Egmond

2015

Immunological Reviews

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100

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Immunoglobulin A (IgA) is the most prevalent antibody at mucosal sites, and has an important role in defense by preventing invasion of pathogens. Traditionally, IgA has been thought of as a non-inflammatory antibody that helps to maintain homeostasis in the mucosa. However, in the last decade it has become clear that IgA is a very potent stimulus to initiate pro-inflammatory cellular processes, especially after triggering the IgA Fc receptor (FcαRI) on neutrophils. It was furthermore described that FcαRI acts as a regulator between anti- and pro-inflammatory responses of IgA. Although neutrophil activation is beneficial in (mucosal) infections, abnormal or excessive IgA immune complexes can induce disproportionate neutrophil migration and in this way initiate a perpetuating neutrophil recruitment and activation loop, which will result in severe tissue damage. Increasing evidence on this process plays a detrimental role in several diseases, including autoimmune IgA blistering diseases, a subtype of rheumatoid arthritis and ulcerative colitis. Inhibiting FcαRI-mediated activation may dampen inflammation in these patients. This process also opens up the possibility of targeting FcαRI in antibody immunotherapy of cancer. Thus, interfering with IgA-mediated FcαRI activation may represent an attractive novel therapeutic strategy for multiple maladies.

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Section: Expression and Structure Of Fcαrimentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The era of the immunoglobulin A Fc receptor FcαRI; its function and potential as target in disease

Aleyd

Heineke

Egmond

2015

Immunological Reviews

Self Cite

100

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“…The functions of these receptors are further reviewed elsewhere [10,20]. In this review, we focus on the IgA Fc receptor (FcaRI, CD89), which is the prototypic and best characterized IgA receptor.…”

Section: Iga and Fcarimentioning

confidence: 99%

Immunoglobulin A: magic bullet or Trojan horse?

Heineke

Egmond

2017

Eur J Clin Investigation

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Background Neutrophils participate in the first line of defense by executing several killing mechanisms, including phagocytosis, degranulation and the release of neutrophil extracellular traps. Additionally, they can orchestrate the adaptive immune system by secreting cytokines and chemokines. Opsonization with antibodies aids in the recognition of pathogens, via binding to Fc receptors on the neutrophil surface. Immunoglobulin A (IgA) is the most abundant antibody at mucosal sites and has multiple functions in homeostasis and immunity. Neutrophils and IgA can interact via the IgA Fc receptor FcRI (CD89), leading to pro-or anti-inflammatory responses.

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“…Expression of receptors for Ig on the surface of epithelial cells is essential for selective internalization, transcellular Ig transport, and intracellular neutralization of several viruses [19-21]. Epithelial Ig receptors can also internalize and transport Igs complexed with viruses or other antigens [23].…”

Section: Discussionmentioning

confidence: 99%

“…Several laboratories have reported that the ability of antibodies to neutralize certain viruses can be extended to intracellular interactions. Internalized antibodies of IgA or IgG isotypes effectively interfere with the replication of these viruses [16-19] due to the fact that mucosal epithelial cells express receptors specific for immunoglobulins (Ig), which mediate their internalization [20, 21]. Epithelial cells of the female genital tract express FcRn, which is responsible for the selective transport of IgG in mucosal secretions [16, 22, 23].…”

Section: Introductionmentioning

confidence: 99%

Characterization of serum antibodies from women immunized with Gardasil: A study of HPV-18 infection of primary human keratinocytes

Wang

Wei

Moldoveanu

et al. 2016

Vaccine

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The prevalent human papillomaviruses (HPVs) infect human epithelial tissues. Infections by the mucosotropic HPV genotypes cause hyperproliferative ano-genital lesions. Persistent infections by high-risk (HR) HPVs such as HPV-16, HPV-18 and related types can progress to high grade intraepithelial neoplasias and cancers. Prophylactic HPV vaccines are based on DNA-free virus-like particles (VLPs) composed of the major capsid protein L1 of HPV-16, -18, -6 and -11 (Gardasil) or HPV-16 and -18 (Cervarix). Sera from vaccinated animals effectively prevent HPV pseudovirions to infect cell lines and mouse cervical epithelia. Both vaccines have proven to be highly protective in people. HPV pseudovirions are assembled in HEK293TT cells from matched L1 and L2 capsid proteins to encapsidate a reporter gene. Pseudovirions and genuine virions have structural differences and they infect cell lines or primary human keratinocytes (PHKs) with different efficiencies. In this study, we show that sera and isolated IgG from women immunized with Gardasil prevent authentic HPV-18 virions from infecting PHKs, whereas non-immune sera and purified IgG thereof are uniformly ineffective. Using early passage PHKs, neutralization is achieved only if immune sera are added within 2 to 4 h of infection. We attribute the timing effect to a conformational change in HPV virions, thought to occur upon initial binding to heparan sulfate proteoglycans (HSPG) on the cell surface. This interpretation is consistent with the inability of immune IgG bound to or taken up by PHKs to neutralize the virus. Interestingly, the window of neutralization increases to 12 to 16 h in slow growing, late passage PHKs, suggestive of altered cell surface molecules. In vivo, this window might be further lengthened by the time required to activate the normally quiescent basal cells to become susceptible to infection. Our observations help explain the high efficacy of HPV vaccines.

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Fc Receptors in Mucosal Immunology

Cited by 7 publications

References 231 publications

The era of the immunoglobulin A Fc receptor FcαRI; its function and potential as target in disease

The era of the immunoglobulin A Fc receptor FcαRI; its function and potential as target in disease

Immunoglobulin A: magic bullet or Trojan horse?

Characterization of serum antibodies from women immunized with Gardasil: A study of HPV-18 infection of primary human keratinocytes

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