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(pituitary adenylate cyclase activating polypeptide) is a widespread neuropeptide with cytoprotective and anti-inflammatory effects. It plays a role in innate and adaptive immunity, but data are limited about gut-associated lymphoid tissue. We aimed to reveal differences in Peyer\u2019s patches between wild-type (WT) and PACAP-deficient (KO) mice. Peyer\u2019s patch morphology from young (3-months-old) and aging (12\u201315-months-old) mice was examined, along with flow cytometry to assess immune cell populations, expression of checkpoint molecules (PD-1, PD-L1, TIM-3, Gal-9) and functional markers (CD69, granzyme B, perforin) in CD3+, CD4+, and CD8+ T cells. We found slight differences between aging, but not in young, WT, and KO mice. In WT mice, aging reduced CD8+ T cell numbers frequency and altered checkpoint molecule expression (higher TIM-3, granzyme B; lower Gal-9, CD69). CD4+ T cell frequency was higher with similar checkpoint alterations, indicating a regulatory shift. In PACAP KO mice, aging did not change cell population frequencies but led to higher TIM-3, granzyme B and lower PD-1, PD-L1, Gal-9, and CD69 expression in CD4+ and CD8+ T cells, with reduced overall T cell activity. Thus, PACAP deficiency impacts immune dysfunction by altering checkpoint molecules and T cell functionality, particularly in CD8+ T cells, suggesting complex immune responses by PACAP, highlighting its role in intestinal homeostasis and potential implications for inflammatory bowel diseases.<\/jats:p>","DOI":"10.3390\/ijms251910676","type":"journal-article","created":{"date-parts":[[2024,10,3]],"date-time":"2024-10-03T10:31:13Z","timestamp":1727951473000},"page":"10676","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Effects of PACAP Deficiency on Immune Dysfunction and Peyer\u2019s Patch Integrity in Adult Mice"],"prefix":"10.3390","volume":"25","author":[{"given":"Jason","family":"Sparks","sequence":"first","affiliation":[{"name":"Department of Anatomy, HUN-REN-PTE PACAP Research Team, Centre for Neuroscience, Medical School, University of Pecs, 7624 Pecs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9913-2024","authenticated-orcid":false,"given":"Matyas","family":"Meggyes","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, Medical School, University of Pecs, 7624 Pecs, Hungary"},{"name":"Janos Szentagothai Research Center, 7624 Pecs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9764-4763","authenticated-orcid":false,"given":"Lilla","family":"Makszin","sequence":"additional","affiliation":[{"name":"Janos Szentagothai Research Center, 7624 Pecs, Hungary"},{"name":"Institute of Bioanalysis, Medical School, University of Pecs, 7624 Pecs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktoria","family":"Jehn","sequence":"additional","affiliation":[{"name":"Department of Anatomy, HUN-REN-PTE PACAP Research Team, Centre for Neuroscience, Medical School, University of Pecs, 7624 Pecs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hedvig","family":"Lugosi","sequence":"additional","affiliation":[{"name":"Department of Anatomy, HUN-REN-PTE PACAP Research Team, Centre for Neuroscience, Medical School, University of Pecs, 7624 Pecs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dora","family":"Reglodi","sequence":"additional","affiliation":[{"name":"Department of Anatomy, HUN-REN-PTE PACAP Research Team, Centre for Neuroscience, Medical School, University of Pecs, 7624 Pecs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1208-2969","authenticated-orcid":false,"given":"Laszlo","family":"Szereday","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, Medical School, University of Pecs, 7624 Pecs, Hungary"},{"name":"Janos Szentagothai Research Center, 7624 Pecs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1007\/s11894-019-0705-6","article-title":"Evolving Epidemiology of IBD","volume":"21","author":"Windsor","year":"2019","journal-title":"Curr. 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