The Role and Function of Fcγ Receptors on Myeloid Cells

Bournazos, Stylianos; Wang, Taia T.; Ravetch, Jeffrey V.

doi:10.1128/microbiolspec.mchd-0045-2016

Cited by 103 publications

(76 citation statements)

References 223 publications

(287 reference statements)

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“…Moreover, cross-linking of FccRs initiates phosphorylation and downstream signaling cascades. 41 Signaling events related to the engagement of FccRs lead to the transcriptional activation of several cytokine and chemokine genes, which-depending on the quality of IgG-FccRs interactions-directs cells into either a pro-or an antiinflammatory state. 42 In murine macrophages, FccR- mediated stimulation of MAPK pathways, particularly the activation of p42 MAPK (also known as ERK2) results in TNF synthesis.…”

Section: Discussionmentioning

confidence: 99%

Antibody opsonization enhances MAIT cell responsiveness to bacteria via a TNF‐dependent mechanism

et al. 2019

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Mucosal‐associated invariant T (MAIT) cells are an abundant human T‐cell subset with antimicrobial properties. They can respond to bacteria presented via antigen‐presenting cells (APCs) such as macrophages, which present bacterially derived ligands from the riboflavin synthesis pathway on MR1. Moreover, MAIT cells are also highly responsive to cytokines which enhance and even substitute for T‐cell receptor‐mediated signaling. The mechanisms leading to an efficient presentation of bacteria to MAIT cells by APCs have not been fully elucidated. Here, we showed that the monocytic cell line THP‐1 and B cells activated MAIT cells differentially in response to Escherichia coli. THP‐1 cells were generally more potent in inducing IFNγ and IFNγ/TNF production by MAIT cells. Furthermore, THP‐1, but not B, cells produced TNF upon bacterial stimulation, which in turn supported IFNγ production by MAIT cells. Finally, we addressed the role of antibody‐dependent opsonization of bacteria in the activation of MAIT cells using in vitro models. We found that opsonization had a substantial impact on downstream MAIT cell activation by monocytes. This was associated with enhanced activation of monocytes and increased TNF release. Importantly, this TNF acted in concert with other cytokines to drive MAIT cell activation. These data indicate both a significant interaction between adaptive and innate immunity in the response to bacteria, and an important role for TNF in MAIT cell triggering.

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Section: Discussionmentioning

confidence: 99%

Antibody opsonization enhances MAIT cell responsiveness to bacteria via a TNF‐dependent mechanism

et al. 2019

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“…The present study further showed a correlation between CD64 expression on circulating neutrophils and SES-CD in adult CD patients with endoscopic active disease only, illustrating a specific relation between levels of CD64 expression on circulating neutrophils and the extent of mucosal lesions in the small and large intestine. As CD64 may be expressed on immune cell types other than neutrophils [53], morphological studies of highly purified cells from inflamed colon were valuable to ascertain that our gating strategy was restricted to the detection of neutrophils and not eosinophils. Notably, CD64 expression was elevated in mucosa relative to blood neutrophils in both CD and healthy individuals and, unexpectedly, higher expression was detected in mucosa of healthy subjects when compared to CD patients.…”

Section: Discussionmentioning

confidence: 99%

Recruitment of activated neutrophils correlates with disease severity in adult Crohn’s disease

Therrien

Chapuy

Bsat

et al. 2018

Clinical and Experimental Immunology

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Summary Neutrophils are detected in inflamed colon in Crohn’s disease (CD). However, whether the frequency and/or activation of circulating or gut tissue neutrophils correlate with endoscopic severity remains to be investigated. A cohort of 73 CD patients was prospectively enrolled according to endoscopic severity and treatment history. Individuals with active disease were stratified using the Montreal classification. Harvey–Bradshaw Index (HBI) and Simple Endoscopic Score for Crohn’s Disease (SES‐CD) were performed at the time of ileocolonoscopy. Frequency of neutrophils and their expression of CD66b and CD64 were assessed in paired blood and colonic biopsies using flow cytometry. The percentage of neutrophils increased in inflamed colon and correlated with SES‐CD in the entire cohort of patients examined, as well as in the subgroup with inflammatory (B1) active disease. SES‐CD further correlated with neutrophil CD66b expression in mucosa but not blood and, conversely, with neutrophil CD64 expression in blood but not mucosa. However, the evaluation of neutrophil activation in mucosa when compared to blood reflected disease activity more clearly. Finally, a neutrophil activation power index (CD66b in mucosa X CD64 in blood) that correlated with SES‐CD discriminated between patients with mild and severe disease. In conclusion, the frequency and activation of colonic neutrophils correlated with SES‐CD, highlighting that mucosal neutrophils are associated with disease severity in CD.

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“…These gamma chains are also a shared subunit of other Fc receptors and are encoded by the fcer1g gene, which contains five exons and spans four kilobases. This gene evolved from the same ancestor as the zeta chain of T cell receptors; both of these genes are located on the long arm of chromosome 1 (1q21-23) [13,[19][20][21], as shown in Table 1.…”

Section: Structure Of Fcγrsmentioning

confidence: 99%

“…Summary of human and murine Fc receptor biology. This table was compiled using information from[19,27,[30][31][32][33].…”

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confidence: 99%

The Diverse Functions of the Ubiquitous Fcγ Receptors and Their Unique Constituent, FcRγ Subunit

Hamdan

Lang

2020

Pathogens

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Fc gamma receptors (FcγRs) are widely expressed on a variety of immune cells and play a myriad of regulatory roles in the immune system because of their structural diversity. Apart from their indispensable role in specific binding to the Fc portion of antibody subsets, FcγRs manifest diverse biological functions upon binding to their putative ligands. Examples of such manifestation include phagocytosis, presentation of antigens, mediation of antibody-dependent cellular cytotoxicity, anaphylactic reactions, and the promotion of apoptosis of T cells and natural killer cells. Functionally, the equilibrium between activating and inhibiting FcγR maintains the balance between afferent and efferent immunity. The γ subunit of the immunoglobulin Fc receptor (FcRγ) is a key component of discrete immune receptors and Fc receptors including the FcγR family. Furthermore, FcγRs exert a key role in terms of crosslinking the innate and adaptive workhorses of immunity. Ablation of one of these receptors might positively or negatively influence the immune response. Very recently, we discovered that FcRγ derived from natural cytotoxicity triggering receptor 1 (NCR1) curtails CD8+ T cell expansion and thereby turns an acute viral infection into a chronic one. Such a finding opens a new avenue for targeting the FcγRs as one of the therapeutic regimens to boost the immune response. This review highlights the structural heterogeneity and functional diversity of the ubiquitous FcγRs along with their featured subunit, FcRγ.

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The Role and Function of Fcγ Receptors on Myeloid Cells

Cited by 103 publications

References 223 publications

Antibody opsonization enhances MAIT cell responsiveness to bacteria via a TNF‐dependent mechanism

Antibody opsonization enhances MAIT cell responsiveness to bacteria via a TNF‐dependent mechanism

Recruitment of activated neutrophils correlates with disease severity in adult Crohn’s disease

The Diverse Functions of the Ubiquitous Fcγ Receptors and Their Unique Constituent, FcRγ Subunit

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