{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n The FCER1G gene encodes the common gamma chain that plays a critical role as an immunoreceptor signaling adaptor across a variety of hematopoietic cells. In plasmacytoid dendritic cells, FCER1G associates with receptors such as ILT7 and BDCA2 to assemble complexes that initiate ITAM‐mediated signals leading to activation of Src family kinases and Syk, which in turn modulate type I interferon and proinflammatory cytokine production."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In engineered immunoreceptor systems, such as those used to redirect T cells against tumor antigens or to enhance natural killer cell functions, the incorporation of FCER1G as the intracellular signaling domain confers cytolytic activity and cytokine secretion via ITAM‐based pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Furthermore, in conditions where the canonical T cell receptor subunit is deficient, as observed in systemic lupus erythematosus, compensatory up‐regulation of FCER1G contributes to enhanced calcium fluxing and signaling through recruitment of Syk, thereby altering T cell activation dynamics."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond lymphocytes, the FCER1G chain is essential in other immune cells. In platelets, it couples to receptors such as GPVI to mediate activation cascades that influence thrombus formation without overt bleeding under physiological conditions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " In mast cells and basophils, FCER1G is required for the full activation response—promoting mediator release such as histamine, leukotrienes, and interleukins—which underpins aspects of allergic inflammation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Moreover, in osteoclastogenesis triggered by inflammatory cytokine combinations, signaling via FCER1G (often referred to as Fcrg in this context) contributes to bone-resorptive processes"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": ", while in allergic rhinitis, mast cell functions that depend on high-affinity IgE receptor complexes require its presence for optimal epithelial responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the cancer setting, notably in clear cell renal cell carcinoma, elevated FCER1G expression is highly correlated with disease progression and adverse prognosis, suggesting that its role in modulating immune-related pathways may extend to tumor biology."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": " Additionally, genetic variants in FCER1G have been implicated in modifying the risk for food sensitization within a context of vitamin D deficiency, highlighting a gene–environment interaction in allergic disease development."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, receptors expressed on dendritic cells that drive immune activation, such as DCAR, also signal via association with FCER1G, further illustrating its broad usage by diverse immunoreceptors to transduce activating signals."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings demonstrate that FCER1G functions as a pivotal adaptor subunit for ITAM-based signaling in multiple immune cell types. 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