{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T21:15:06Z","timestamp":1768252506486,"version":"3.49.0"},"reference-count":41,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,12,13]],"date-time":"2019-12-13T00:00:00Z","timestamp":1576195200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Rep Immunol"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Problem<\/jats:title><jats:p>Pituitary adenylate cyclase\u2010activating polypeptide (PACAP) is a neuropeptide having several regulatory functions in the nervous system and in peripheral organs including those of the reproductive system. PACAP\u2010deficient male mice have several morphological, biochemical, behavioral defects and show disturbed signaling in spermatogenesis affecting fertility in PACAP KO mice. Reproductive functions such as fertility, mating, and maternal behaviors have been widely investigated, but no immune analyses are available regarding the testicular immune\u2010privileged environment in male PACAP\u2010deficient mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method of Study<\/jats:title><jats:p>We performed detailed immunophenotyping of testicular immune cells and investigated the expression of TIM\u20103 and PD\u20101 Immune checkpoint molecules of immune cells together with the detection of galectin\u20109 and perforin. We investigated the percentage of numerous immune cell populations in the testis of wild\u2010type and PACAP\u2010deficient mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We demonstrated a significant increase in the frequency of testicular CD8+ T cells together with the decrease in Treg cell number obtained from PACAP KO mice compared with wild\u2010type mice. Investigating Immune checkpoint receptors, only PD\u20101 showed a significantly decreased expression in CD8+ T cells in PACAP KO mice compared with wild\u2010type suggesting an impaired PD\u20101\/PD\u2010L1 pathway. Regarding TIM\u20103 expression, we did not find any significant difference between the investigated groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We hypothesize that these local changes may result in an immune activation with disturbed testicular immunoregulation in PACAP KO mice; however, determining the exact function requires further investigations. Our data further support the view that besides a systemic immune tolerance, localized active immunosuppression is involved in the regulation of testicular immune privilege.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aji.13212","type":"journal-article","created":{"date-parts":[[2019,11,23]],"date-time":"2019-11-23T07:19:51Z","timestamp":1574493591000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Phenotypic characterization of testicular immune cells expressing immune checkpoint molecules in wild\u2010type and pituitary adenylate cyclase\u2010activating polypeptide\u2010deficient mice"],"prefix":"10.1111","volume":"83","author":[{"given":"Matyas","family":"Meggyes","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology and Immunology Medical School University of Pecs Pecs Hungary"},{"name":"Janos Szentagothai Research Center Pecs 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