{"type": "root", "children": [{"type": "t", "text": "<div>\n "}, {"type": "p", "children": [{"type": "t", "text": "\n IL12RB2 encodes the interleukin‐12 receptor β2 subunit, a critical component of multiple cytokine receptor complexes that orchestrate distinct immune responses. In conventional T cells, IL12RB2 is upregulated by IL‐2–mediated STAT5 activation, enabling IL‐12 signaling that drives T helper 1 (Th1) differentiation and interferon‐γ production. This finely tuned regulation is essential for host defense against intracellular pathogens, as patients with congenital IL12RB2 deficiency develop mycobacterial infections despite intact responses to other cytokines."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In regulatory T cells, a delayed induction of IL12RB2 helps prevent premature or excessive Th1 programming, thereby preserving their suppressive capacity during type 1 inflammatory responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its canonical role in IL‐12 signaling, IL12RB2 functions as a key receptor subunit for interleukin‐35 (IL‐35). In complex with gp130, IL12RB2 mediates IL‐35–induced signals that suppress conventional T cell proliferation and promote the conversion of naïve T cells into induced regulatory T cells. This unique heterodimeric IL‐35 receptor signals through STAT1 and STAT4 and has been implicated in immunosuppressive pathways that can influence tumor behavior—for example, by enabling cancer cells, after epithelial–mesenchymal transition, to become responsive to IL‐35, thereby facilitating metastatic colonization, and by promoting pro‐angiogenic transcriptional programs in monocytes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Furthermore, genome‐wide association studies have identified genetic variants in or near IL12RB2 that confer susceptibility to a variety of autoimmune conditions—including psoriasis, Behçet’s disease, and primary biliary cirrhosis—highlighting the pivotal role of IL12RB2 in maintaining immune homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, IL12RB2 plays multifaceted roles in immune regulation by modulating Th1 differentiation and interferon‐γ responses via IL‐12 signaling, by integrating into the IL‐35 receptor complex to propagate immunosuppressive signals, and by being subject to genetic variation that influences susceptibility to autoimmune and inflammatory diseases.\n "}]}, {"type": "t", "text": "\n</div>"}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Wei Liao, Jian-Xin Lin, Lu Wang, et al. 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