{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNFAM1, originally characterized as a calcineurin/NFAT‐activating and ITAM‐containing protein (also referred to as CNAIP), is a novel transmembrane receptor predominantly expressed in immune‐related cells such as neutrophils, monocytes, and mast cells. Experimental studies in cell models have demonstrated that NFAM1 activates the calcineurin/NFAT signaling cascade to drive the transcription of key cytokine genes (e.g., interleukin‐13 and tumor necrosis factor‐α) in an ITAM‐dependent manner."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn vivo investigations have further linked NFAM1 to the amplification of inflammatory responses. Analysis of human intestinal biopsies from patients with Crohn’s disease and ulcerative colitis revealed a marked upregulation of NFAM1, with high expression levels noted in monocytes and neutrophils. Functional studies using NFAM1‐deficient mice and human monocytes showed that deletion of NFAM1 significantly attenuated the production of multiple pro‐inflammatory cytokines and chemokines—including TNF‐α, IL‐6, IL‐12, CCL3, and CCL4—in response to stimuli such as CD40L, toll‐like receptor ligands, and MDP. Moreover, emerging evidence indicates that NFAM1 expressed on circulating monocytes is implicated in the inflammatory milieu that underpins coronary artery disease."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAdditional mechanistic insights have come from studies on myocardial infarction, where NFAM1 expression is indirectly regulated by non‐coding RNA. In this context, a circular RNA derived from the ITGB1 gene (circITGB1) is enriched in extracellular vesicles and functions as a sponge for miR‑342‑3p, thereby relieving its repression of NFAM1. The upregulation of NFAM1 consequent to circITGB1 action promotes dendritic cell maturation and exacerbates cardiac damage, linking NFAM1 to the pathogenesis of acute myocardial infarction."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jianhua Yang, Guanghui Hu, Shen-Wu Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Calcineurin/nuclear factors of activated T cells (NFAT)-activating and immunoreceptor tyrosine-based activation motif (ITAM)-containing protein (CNAIP), a novel ITAM-containing protein that activates the calcineurin/NFAT-signaling pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M211060200"}], "href": "https://doi.org/10.1074/jbc.M211060200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12615919"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12615919"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jie Long, Jiemei Chen, Qingchun Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NFAT activating protein with ITAM motif 1 (NFAM1) is upregulated on circulating monocytes in coronary artery disease and potentially correlated with monocyte chemotaxis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Atherosclerosis (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.atherosclerosis.2020.06.001"}], "href": "https://doi.org/10.1016/j.atherosclerosis.2020.06.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32711213"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32711213"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Kathryn W Juchem, Anshu P Gounder, Jian Ping Gao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NFAM1 Promotes Pro-Inflammatory Cytokine Production in Mouse and Human Monocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Front Immunol (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3389/fimmu.2021.773445"}], "href": "https://doi.org/10.3389/fimmu.2021.773445"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35095847"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35095847"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Jianbing Zhu, Zhaoyang Chen, Xiaoping Peng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Extracellular Vesicle-Derived circITGB1 Regulates Dendritic Cell Maturation and Cardiac Inflammation via miR-342-3p/NFAM1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oxid Med Cell Longev (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1155/2022/8392313"}], "href": "https://doi.org/10.1155/2022/8392313"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35615580"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35615580"}]}]}]}