Abstract:Anti-glycan/ganglioside antibodies are the most common immune effectors found in patients with Guillain-Barré Syndrome, which is a peripheral autoimmune neuropathy. We previously reported that disease-relevant anti-glycan autoantibodies inhibited axon regeneration, which echo the clinical association of these antibodies and poor recovery in Guillain-Barré Syndrome. However, the specific molecular and cellular elements involved in this antibody-mediated inhibition of axon regeneration are not previously defined… Show more
“…These studies provide further experimental evidence of the role of macrophages and activating FcγRs mediated-inflammation in Ab-mediated experimental models of autoimmune neuropathies. In line with these animal studies, we also found that macrophages and Schwann cells do express FcγR common chain in the nerves of patients with axonal GBS [43]. The FcγR common chain expression was significantly upregulated in GBS nerves compared to controls and activated macrophages expressing activating FcγRs were found adjacent to widened nodes in axonal GBS patient nerves (Figure 1).…”
Section: Journal Of Clinical and Cellular Immunologysupporting
confidence: 83%
“…Our studies in op/op mice confirmed the involvement of macrophages in AGA-mediated pathological effects in this model [43]. In order to dissect the contribution of FcγRs-bearing circulating macrophage and FcγRs-expressing resident endoneurial glial cells, a nerve grafting study, in which wild type (WT) or activating FcγRs-null (Fcer1g-/-) nerve segments (donors) were transplanted in background matched WT or Fcer1g-/-(hosts) mice, was carried out [43]. We found that there is significantly more axon regeneration in WT or FcγRs-null grafts implanted in FcγRs-null hosts, compared to WT or FcγRs-null grafts implanted in WT hosts.…”
Section: Journal Of Clinical and Cellular Immunologysupporting
confidence: 82%
“…We showed that passive transfer of AGAs (experimental and human) impair nerve repair and severely inhibit axon regeneration, and ICs formed by AGA and its target antigen is required for the inhibition in nerve crush model [19,42,43]. These experimental findings echo the clinical association of AGAs and poor recovery in GBS.…”
Section: Journal Of Clinical and Cellular Immunologymentioning
“…These studies provide further experimental evidence of the role of macrophages and activating FcγRs mediated-inflammation in Ab-mediated experimental models of autoimmune neuropathies. In line with these animal studies, we also found that macrophages and Schwann cells do express FcγR common chain in the nerves of patients with axonal GBS [43]. The FcγR common chain expression was significantly upregulated in GBS nerves compared to controls and activated macrophages expressing activating FcγRs were found adjacent to widened nodes in axonal GBS patient nerves (Figure 1).…”
Section: Journal Of Clinical and Cellular Immunologysupporting
confidence: 83%
“…Our studies in op/op mice confirmed the involvement of macrophages in AGA-mediated pathological effects in this model [43]. In order to dissect the contribution of FcγRs-bearing circulating macrophage and FcγRs-expressing resident endoneurial glial cells, a nerve grafting study, in which wild type (WT) or activating FcγRs-null (Fcer1g-/-) nerve segments (donors) were transplanted in background matched WT or Fcer1g-/-(hosts) mice, was carried out [43]. We found that there is significantly more axon regeneration in WT or FcγRs-null grafts implanted in FcγRs-null hosts, compared to WT or FcγRs-null grafts implanted in WT hosts.…”
Section: Journal Of Clinical and Cellular Immunologysupporting
confidence: 82%
“…We showed that passive transfer of AGAs (experimental and human) impair nerve repair and severely inhibit axon regeneration, and ICs formed by AGA and its target antigen is required for the inhibition in nerve crush model [19,42,43]. These experimental findings echo the clinical association of AGAs and poor recovery in GBS.…”
Section: Journal Of Clinical and Cellular Immunologymentioning
“…This observation may therefore relate to the potent immune stimulating activity of mAb targeting TNF receptor super family members such as CD40 and DR4/5 (12)(13)(14)50). In contrast to direct targeting mAb such as rituximab, which are impaired by mFcgRII and hFcgRIIB, these receptors are now known to be an important component of immunomodulatory mAb activity, where they serve to further cross-link the target receptor for optimal signaling (20)(21)(22)(23)(24)(25)reviewed in Ref. 26).…”
Section: Discussionmentioning
confidence: 99%
“…Heterozygous mFcgRIV +/2 mice, from the European Conditional Mouse Mutagenesis Program consortia distributed by the Helmholtz Zentrum M€ unchen (Munich, Germany), have been described previously (23) and were intercrossed to obtain mFcgRIV 2/2 . All strains were backcrossed onto the BALB/c or C57BL/6J background for at least 10 generations.…”
FcγRs are key regulators of the immune response, capable of binding to the Fc portion of IgG Abs and manipulating the behavior of numerous cell types. Through a variety of receptors, isoforms, and cellular expression patterns, they are able to fine-tune and direct appropriate responses. Furthermore, they are key determinants of mAb immunotherapy, with mAb isotype and FcγR interaction governing therapeutic efficacy. Critical to understanding the biology of this complex family of receptors are reagents that are robust and highly specific for each receptor. In this study, we describe the development and characterization of mAb panels specific for both mouse and human FcγR for use in flow cytometry, immunofluorescence, and immunocytochemistry. We highlight key differences in expression between the two species and also patterns of expression that will likely impact on immunotherapeutic efficacy and translation of therapeutic agents from mouse to clinic.
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