Evidence for neuronal expression of functional Fc (ε and γ) receptors

Abstract

The Fc receptor family plays a key role in adaptive immunity through the binding of immunoglobulin antibodies that recognize an immune insult and elicit an inflammatory response leading to its clearance. Dysregulation of this receptor family may have untoward consequences that result in autoimmune and allergic diseases. Many of these diseases seem to involve the nervous system and are exacerbated by stress or other neurological challenges. Recently, the presence of Fc receptors was uncovered on dorsal root ganglion neurons and suggested an IgG and possibly IgE-mediated activation of neurons 1-3 . We set out to more extensively explore which Fc receptors might be expressed in neurons, and whether they were functional and able to transmit signals to interconnected neurites in vitro and in vivo Messenger RNA was isolated from a highly pure culture of mouse superior cervical ganglion (SCG) neurons 4 and expression of Fc receptor transcripts assessed by reverse transcriptasepolymerase chain reactions (RT-PCR) using specific primers for Fcγ and Fcε family members. Fig. 1,a demonstrates the presence of transcripts for the immunoglobulin-binding α chain of FcγRI, II, III, and IV in three individual SCG neuron mRNA preparations. A small amount of the transcript for the low affinity IgE receptor (FcεRII or CD23) was also detected relative to Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. that seen in B cells, known to express this receptor. FcγRI transcripts were detected in bone marrow derived mouse mast cells but these levels were less than seen in the neurons. This observation and the inability to detect mMCP-6mRNA in either Balb/c or Bl6 mice, together with the absence of CD23 transcripts in both neurons and mast cells provided confidence that the observed Fc receptor transcripts in neurons was not a result of mast cell contamination of cultures. NIH Public AccessWe also unexpectedly observed the presence of transcripts for the α, β, and γ chains of the high affinity IgE receptor (FcεRI) (Fig. 1,b). While the trimeric form (αγ 2 ) of this receptor has been described in cells other than mast cells or basophils (such as in human Langerhans cells 5), the expression of the tetrameric form (αβγ 2 ) was previously thought to be limited to these proinflammatory cells. The trimeric FcεRI shows weak calcium signals when compared to the tetrameric form due to the absence of the FcεRIβ in the former 6 . To determine if the FcεRI was expressed on the cell surface of SCG neurons, cells were incubated with IgE and with an antibody to the neuronal specific protein gene product (PGP) 9.5 (whi...

Neuronal Fc-gamma receptor I mediated excitatory effects of IgG immune complex on rat dorsal root ganglion neurons

“…Recent studies revealed the presence of FcγRI on both DRG (Andoh and Kuraishi, 2004) and superior cervical ganglion neurons of mice (van der Kleij et al, 2010). The present study showed that FcγRI, but not FcγRII or FcγRIII, is expressed on a subpopulation of rat DRG neurons, consistent with previous reports (Andoh and Kuraishi, 2004).…”

Non-pathogenic tissue-resident CD8+ T cells uniquely accumulate in the brains of lupus-prone mice

“…We propose that in the absence of brain-resident CD8 + T cells, unrestricted CD4 + T cell activity and IgE production could be responsible for disease aggravation in lupus-prone mice. Interestingly, the high affinity IgE receptor, FcεRI, was recently shown to be expressed on neurons59, which indicates that any IgE entering the brain has the potential to induce a local inflammatory response. While it is clear that CD8 + T cells are required to regulate the antibody response in TLR7[Tg] lupus-prone mice, more studies will need to be performed to fully elucidate any regulatory mechanism that may be imparted by these brain-resident CD8 + T cells and determine if they are similar in function to memory cells previously described in models of viral or bacterial infection.…”

p-Tau immunotherapy reduces soluble and insoluble tau in aged 3xTg-AD mice

“…Another possibility, also barrowing from observations from studies targeting Aβ, is that unbound antibody can enter neurons: targeting tau directly within the cells. Neurons have been shown to possess receptors that can bind and internalize IgG [27], and thus, could actively internalized antibodies to tau, which would then subsequently target intraneuronal pools of aggregated tau. Once the antibody-tau complex is formed, it has been hypothesized that a final destination is likely the endosomal/lysosomal system for degradation [22].…”