{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nIn studies of aged mouse models, a chitinase‐like protein—referred to in these reports as Ym2 (also known as Chi3l4)—was identified as a major constituent of hyaline lesions found in tissues such as the glandular stomach, respiratory tract, bile duct, and gall bladder. The accumulation of Ym2 in these lesions suggests that its associated transcript, here linked to MIF4GD-DT, may play a role in extracellular matrix remodeling and in modulating local inflammatory processes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the allergic lung, Ym2 is robustly expressed in an IL-13–dependent manner by dendritic cells, where it helps promote Th2 cytokine production. Mechanistically, Ym2 interacts with 12/15-lipoxygenase to inhibit the production of 12(S)-HETE—a metabolite that normally dampens Th2 responses—thereby enhancing the secretion of key allergic mediators such as IL-5 and IL-13. This suggests a role for MIF4GD-DT–related pathways in fine-tuning immune responses during allergic inflammation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nParallel investigations in dermatologic conditions reveal that expression of Ym2 is markedly upregulated in inflammatory skin diseases, including chronic proliferative dermatitis and contact hypersensitivity. The dramatic increase in Ym2 mRNA and protein levels, particularly compared with its isotype Ym1, underscores its potential involvement in modulating immune cell functions—especially in macrophages, dendritic cells, and mast cells—in the context of cutaneous inflammation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nStudies focused on mast cell biology further demonstrate that Ym2 expression is differentially regulated by cytokines. While Ym1 is constitutively expressed in bone marrow cells, Ym2 is specifically induced by IL-4 in connective tissue–type mast cells. This cytokine-dependent induction implies that the MIF4GD-DT–associated pathway, through Ym2, may be crucial in enhancing mast cell functions and possibly in shaping allergic inflammatory outcomes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAdditionally, in the context of neural tissue regeneration, Ym2 plays a pivotal role in the recovery of the injured olfactory epithelium. Injury-induced upregulation of Ym2 in supporting cells accelerates cell proliferation and differentiation, a process that is compromised by anti-inflammatory treatments but can be rescued through its overexpression. This finding links the MIF4GD-DT–associated pathway to the regulation of tissue repair, highlighting an important interplay between inflammatory signals and regenerative capacity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "J M Ward, M Yoon, M R Anver, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hyalinosis and Ym1/Ym2 gene expression in the stomach and respiratory tract of 129S4/SvJae and wild-type and CYP1A2-null B6, 129 mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Pathol (2001)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/S0002-9440(10)63972-7"}], "href": "https://doi.org/10.1016/S0002-9440(10"}, {"type": "t", "text": "63972-7) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11141507"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11141507"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Yeping Cai, Rakesh K Kumar, Jiansheng Zhou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ym1/2 promotes Th2 cytokine expression by inhibiting 12/15(S)-lipoxygenase: identification of a novel pathway for regulating allergic inflammation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.0803874"}], "href": "https://doi.org/10.4049/jimmunol.0803874"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19380786"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19380786"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Harm HogenEsch, Anisa Dunham, Rosemarie Seymour, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of chitinase-like proteins in the skin of chronic proliferative dermatitis (cpdm/cpdm) mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Dermatol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1600-0625.2006.00483.x"}], "href": "https://doi.org/10.1111/j.1600-0625.2006.00483.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16984263"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16984263"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Eunkyung Lee, Jumin Yook, Kyungmi Haa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Induction of Ym1/2 in mouse bone marrow-derived mast cells by IL-4 and identification of Ym1/2 in connective tissue type-like mast cells derived from bone marrow cells cultured with IL-4 and stem cell factor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Immunol Cell Biol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1440-1711.2005.01352.x"}], "href": "https://doi.org/10.1111/j.1440-1711.2005.01352.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16174095"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16174095"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Li Wang, Wenwen Ren, Xuewen Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Chitinase-Like Protein Ym2 (Chil4) Regulates Regeneration of the Olfactory Epithelium via Interaction with Inflammation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/JNEUROSCI.1601-20.2021"}], "href": "https://doi.org/10.1523/JNEUROSCI.1601-20.2021"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34016714"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34016714"}]}]}]}