{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T10:40:02Z","timestamp":1763635202278,"version":"3.45.0"},"reference-count":75,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T00:00:00Z","timestamp":1763596800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"SEP-CONACyT-Mexico","award":["A1-S-53561"],"award-info":[{"award-number":["A1-S-53561"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Teleost fish are the first evolutionary group to exhibit an innate and adaptive immune system. Within the mechanisms of adaptive immunity, fish possess, among others, T-helper cells (CD4-like) and their differentiation machinery, regulated by the master transcription factors T-bet, GATA3, Foxp3, and ROR\u03b3. Many studies support the existence of a non-neuronal cholinergic system involved in the immune response, named after the ability of leukocytes to synthesize de novo acetylcholine (ACh). Organophosphorus pesticides (OPs), such as diazoxon (DXN), are examples of compounds that act as cholinergic disruptors with immunotoxic effects. The present study aimed to evaluate the expression of transcription factors in leukocytes (spleen mononuclear cells, SMNCs) of Nile tilapia by modulating cholinergic pathways in immune cells using agonists, antagonists, and diazoxon (DXN), an anticholinesterase substance. The obtained data showed a significant increase in ROR\u03b3 mRNA expression upon stimulation with the nicotinic agonist, whereas activation of the muscarinic receptor with its agonist increased T-bet mRNA expression. An alteration in ROR\u03b3 expression levels induced by DXN exposure was also observed. The results suggest a probable directing of the immune response towards a pro-inflammatory profile orchestrated mainly by ROR\u03b3 and T-bet transcription factors in response to cholinergic stimuli.<\/jats:p>","DOI":"10.3390\/ijms262211206","type":"journal-article","created":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T10:30:59Z","timestamp":1763634659000},"page":"11206","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Modulation of Master Transcription Factor Expression of Nile Tilapia Leukocytes via Cholinergic Pathways"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6808-6590","authenticated-orcid":false,"given":"Manuel Ivan","family":"Gir\u00f3n-P\u00e9rez","sequence":"first","affiliation":[{"name":"Laboratorio Nacional de Investigaci\u00f3n para la Inocuidad Alimentaria (LANIIA)\u2014Unidad Nayarit, Universidad Aut\u00f3noma de Nayarit, Calle Tres S\/N, Colonia, Cd. Industrial, Tepic Z.C. 63000, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenia Mar\u00eda","family":"Ram\u00edrez-Ibarra","sequence":"additional","affiliation":[{"name":"Laboratorio Nacional de Investigaci\u00f3n para la Inocuidad Alimentaria (LANIIA)\u2014Unidad Nayarit, Universidad Aut\u00f3noma de Nayarit, Calle Tres S\/N, Colonia, Cd. Industrial, Tepic Z.C. 63000, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5396-5357","authenticated-orcid":false,"given":"Carlos Eduardo","family":"Covantes-Rosales","sequence":"additional","affiliation":[{"name":"Laboratorio Nacional de Investigaci\u00f3n para la Inocuidad Alimentaria (LANIIA)\u2014Unidad Nayarit, Universidad Aut\u00f3noma de Nayarit, Calle Tres S\/N, Colonia, Cd. Industrial, Tepic Z.C. 63000, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3262-8279","authenticated-orcid":false,"given":"Daniel Alberto","family":"Gir\u00f3n-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Laboratorio Nacional de Investigaci\u00f3n para la Inocuidad Alimentaria (LANIIA)\u2014Unidad Nayarit, Universidad Aut\u00f3noma de Nayarit, Calle Tres S\/N, Colonia, Cd. Industrial, Tepic Z.C. 63000, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francisco Fabi\u00e1n","family":"Razura-Carmona","sequence":"additional","affiliation":[{"name":"Laboratorio Nacional de Investigaci\u00f3n para la Inocuidad Alimentaria (LANIIA)\u2014Unidad Nayarit, Universidad Aut\u00f3noma de Nayarit, Calle Tres S\/N, Colonia, Cd. Industrial, Tepic Z.C. 63000, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5273-3167","authenticated-orcid":false,"given":"Arturo","family":"Contis-Montes de Oca","sequence":"additional","affiliation":[{"name":"Plan de San Luis y D\u00edaz Mir\u00f3n s\/n, Secci\u00f3n de Estudios de Posgrado, Escuela Superior de Medicina, Instituto Polit\u00e9cnico Nacional, Col. Casco de Santo Tomas, Alcald\u00eda Miguel Hidalgo, Ciudad de M\u00e9xico Z.C. 11340, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9461-610X","authenticated-orcid":false,"given":"Jorge","family":"Morales-Montor","sequence":"additional","affiliation":[{"name":"Departamento de Inmunolog\u00eda, Instituto de Investigaciones Biom\u00e9dicas, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Coyoac\u00e1n, Ciudad de M\u00e9xico Z.C. 04510, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6067-6868","authenticated-orcid":false,"given":"Lenin","family":"Pav\u00f3n","sequence":"additional","affiliation":[{"name":"Laboratorio de Psicoinmunolog\u00eda, Instituto Nacional de Psiquiatr\u00eda Ram\u00f3n de la Fuente Mu\u00f1iz, Ciudad de M\u00e9xico Z.C. 14370, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0990-2871","authenticated-orcid":false,"given":"Gladys Alejandra","family":"Toledo-Ibarra","sequence":"additional","affiliation":[{"name":"Laboratorio Nacional de Investigaci\u00f3n para la Inocuidad Alimentaria (LANIIA)\u2014Unidad Nayarit, Universidad Aut\u00f3noma de Nayarit, Calle Tres S\/N, Colonia, Cd. Industrial, Tepic Z.C. 63000, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3939","DOI":"10.4049\/jimmunol.177.6.3939","article-title":"Evolution of the CD4 Family: Teleost Fish Possess Two Divergent Forms of CD4 in Addition to Lymphocyte Activation Gene-3","volume":"177","author":"Laing","year":"2006","journal-title":"J. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1038\/ni.1913","article-title":"IgT, a primitive immunoglobulin class specialized in mucosal immunity","volume":"11","author":"Zhang","year":"2010","journal-title":"Nat. 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