{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T13:37:58Z","timestamp":1791466678326,"version":"4.3.4"},"reference-count":52,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T00:00:00Z","timestamp":1743379200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"UE","award":["MCIN\/AEI\/10.13039\/501100011033\/FEDER"],"award-info":[{"award-number":["MCIN\/AEI\/10.13039\/501100011033\/FEDER"]}]},{"name":"UE","award":["IDE\/2024-000764"],"award-info":[{"award-number":["IDE\/2024-000764"]}]},{"name":"UE","award":["PRE20200-096451"],"award-info":[{"award-number":["PRE20200-096451"]}]},{"name":"PCTI 2025\u20132026","award":["MCIN\/AEI\/10.13039\/501100011033\/FEDER"],"award-info":[{"award-number":["MCIN\/AEI\/10.13039\/501100011033\/FEDER"]}]},{"name":"PCTI 2025\u20132026","award":["IDE\/2024-000764"],"award-info":[{"award-number":["IDE\/2024-000764"]}]},{"name":"PCTI 2025\u20132026","award":["PRE20200-096451"],"award-info":[{"award-number":["PRE20200-096451"]}]},{"name":"National Institute for Agricultural Research (INIA)","award":["MCIN\/AEI\/10.13039\/501100011033\/FEDER"],"award-info":[{"award-number":["MCIN\/AEI\/10.13039\/501100011033\/FEDER"]}]},{"name":"National Institute for Agricultural Research (INIA)","award":["IDE\/2024-000764"],"award-info":[{"award-number":["IDE\/2024-000764"]}]},{"name":"National Institute for Agricultural Research (INIA)","award":["PRE20200-096451"],"award-info":[{"award-number":["PRE20200-096451"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>Summary-data-based Mendelian randomization (SMR) analysis identified a novel cis-expression quantitative loci (cis-eQTL) associated with the upregulation of the expression of the early growth response factor 4 (EGR4) gene in animals with paratuberculosis (PTB)-associated multifocal lesions, which has been suggested to be modulating the NF-k\u03b2-induced proinflammatory immune response to Mycobacterium avium subsp. paratuberculosis (Map) infection. To confirm these findings and to study the role of EGR4 expression in PTB resilience, the number of EGR4-expressing cells were analysed in paraffin-fixed gut tissues and regional lymph nodes of naturally Map-infected Holstein Friesian cows with focal, multifocal (subclinical and clinical), and diffuse lesions (intermediate and multibacillary), and in controls without lesions by quantitative anti-EGR4 immunohistochemistry. Subclinical animals with multifocal lesions showed a significantly higher number of EGR4-positive cells and were sacrificed at a significantly older average age than the remaining groups (p &lt; 0.001 in all cases). We hypothesize that EGR4 could be mitigating the negative impact of Map infection on host clinical status through its involvement in three molecular mechanisms that promote resilience: (i) limiting NF-k\u03b2-mediated proinflammatory responses, (ii) controlling tissue damage, acting as a brake on T-cell proliferation and cytokine production, and (iii) favouring tissue repair through interaction with epidermal growth factor receptor (EGFR).<\/jats:p>","DOI":"10.3390\/ani15071012","type":"journal-article","created":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T05:29:19Z","timestamp":1743485359000},"page":"1012","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Early Growth Response Factor 4 (EGR4) Expression in Gut Tissues and Regional Lymph Nodes of Cattle with Different Types of Paratuberculosis-Associated Lesions: Potential Role of EGR4 in Resilience to Paratuberculosis"],"prefix":"10.3390","volume":"15","author":[{"given":"Alejandra Isabel","family":"Navarro Le\u00f3n","sequence":"first","affiliation":[{"name":"Center for Animal Biotechnology, Servicio Regional de Investigaci\u00f3n y Desarrollo Agroalimentario (SERIDA), 33394 Deva, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5979-347X","authenticated-orcid":false,"given":"Marta","family":"Alonso-Hearn","sequence":"additional","affiliation":[{"name":"Animal Health Department, NEIKER, Basque Institute for Agricultural Research and Development, Basque Research and Technology Alliance (BRTA), 48160 Alava, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Center for Animal Biotechnology, Servicio Regional de Investigaci\u00f3n y Desarrollo Agroalimentario (SERIDA), 33394 Deva, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Iglesias","sequence":"additional","affiliation":[{"name":"Center for Animal Biotechnology, Servicio Regional de Investigaci\u00f3n y Desarrollo Agroalimentario (SERIDA), 33394 Deva, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8943-2365","authenticated-orcid":false,"given":"Gerard","family":"Badia-Bringu\u00e9","sequence":"additional","affiliation":[{"name":"Animal Health Department, NEIKER, Basque Institute for Agricultural Research and Development, Basque Research and Technology Alliance (BRTA), 48160 Alava, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0208-4880","authenticated-orcid":false,"given":"Tania","family":"Iglesias","sequence":"additional","affiliation":[{"name":"Unidad de Consultor\u00eda Estad\u00edstica, Servicios Cient\u00edfico-T\u00e9cnicos, Universidad de Oviedo, Campus de Gij\u00f3n, 33203 Gij\u00f3n, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Balseiro","sequence":"additional","affiliation":[{"name":"Departamento de Sanidad Animal, Facultad de Veterinaria, Universidad de Le\u00f3n, 24071 Le\u00f3n, Spain"},{"name":"Instituto de Ganader\u00eda de Monta\u00f1a (IGM, CSIC-ULE), 24346 Le\u00f3n, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"Casais","sequence":"additional","affiliation":[{"name":"Center for Animal Biotechnology, Servicio Regional de Investigaci\u00f3n y Desarrollo Agroalimentario (SERIDA), 33394 Deva, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3123","DOI":"10.3168\/jds.2020-19381","article-title":"Economic losses due to Johne\u2019s disease (paratuberculosis) in dairy cattle","volume":"104","author":"Rasmussen","year":"2021","journal-title":"J. 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