{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nThe proteins described in these studies function as modulators of protease activity and immune regulation. Notably, although the initial query mentioned OR13F1, the supplied abstracts discuss CTLA‐2 isoforms, which act as cysteine protease inhibitors with distinct roles in reproductive physiology and immune tolerance. Together, these studies reveal a dual functionality for CTLA‐2 family members in modulating both local tissue remodeling during embryo implantation and systemic immune responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the first study, CTLA‐2β expression was shown to be induced in the decidua during early pregnancy in a progesterone receptor–dependent manner, but only in the context of decidual stimulation. Its expression coincided spatially and temporally with the decidual phase and correlated with the inhibition of cathepsin L, a cysteine protease expressed by trophoblastic cells. This suggests that CTLA‐2β helps regulate proteolytic activity at the maternal–embryo interface, potentially preventing excessive matrix degradation during implantation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nThe second study identified that both isoforms of CTLA‐2 (CTLA‐2α and CTLA‐2β) are upregulated in dendritic cells as they undergo maturation under conditions that favor a tolerogenic phenotype. When induced by cholera toxin at lower doses or by cAMP, these CTLA‐2 molecules enhance TGF‐β–dependent conversion of naïve T cells into Foxp3⁺ induced regulatory T cells, resulting in dampened proinflammatory Th17 responses. This tolerogenic mechanism contributes to protection in an experimental autoimmune encephalomyelitis model and may also reflect an immune evasion strategy exploited by Vibrio cholerae."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yong-Pil Cheon, Francesco J DeMayo, Milan K Bagchi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Induction of cytotoxic T-lymphocyte antigen-2beta, a cysteine protease inhibitor in decidua: a potential regulator of embryo implantation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M309434200"}], "href": "https://doi.org/10.1074/jbc.M309434200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14681235"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14681235"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Cinthia Silva-Vilches, Katrien Pletinckx, Miriam Lohnert, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Low doses of cholera toxin and its mediator cAMP induce CTLA-2 secretion by dendritic cells to enhance regulatory T cell conversion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0178114"}], "href": "https://doi.org/10.1371/journal.pone.0178114"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28759565"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28759565"}]}]}]}