{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T07:29:35Z","timestamp":1790839775516,"version":"4.1.0"},"reference-count":43,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2022,8,16]],"date-time":"2022-08-16T00:00:00Z","timestamp":1660608000000},"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":["Colorectal Disease"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>The aetiology of cryptoglandular anal fistula (AF) is poorly understood. Evidence suggests that persistence and\/or recurrence of the disease is more related to inflammatory than infectious factors. The aim of this study was to investigate the immune profile of cryptoglandular AF and to perform a histopathological characterization.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>Fistulectomy was performed in all patients; healthy ischioanal fat from the same patients was used as a control. Samples were evaluated by the Luminex xMAP system for the detection of 27 analytes. AF tissues were analysed using immunofluorescence. Staining was performed using primary antibodies to identify M1 inflammatory and M2 anti\u2010inflammatory macrophages. Selective staining of total T lymphocytes and different T lymphocyte subsets was performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Twenty patients with AF underwent a fistulectomy. Specific cytokine pathways differentiated AF from healthy tissue: pro\u2010inflammatory cytokines interleukin (IL)\u20101\u03b2, IL\u20104, IL\u20108 and IL\u201017 and the anti\u2010inflammatory cytokine IL\u201010 were overexpressed in AF compared with controls. Chemokines involved in macrophage recruitment (CCL2, CCL3, CCL4) were higher in AF than in healthy fatty tissue. Moreover, we showed that Tc17 cells characterize AF patients, thus confirming the enzyme\u2010linked immunosorbent assay data. Furthermore, elevated infiltration of CD68+ myeloid cells and a reduction of the M1\/M2 ratio characterize AF patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>A combination of inflammatory cytokines, chemokines and growth factors reside in the wound microenvironment of AF patients. For the first time an important prevalence of Tc17 cells and a reduction in the M1\/M2 ratio was observed, thus suggesting new insights into the immunological characterization of AF patients.<\/jats:p><\/jats:sec>","DOI":"10.1111\/codi.16290","type":"journal-article","created":{"date-parts":[[2022,8,2]],"date-time":"2022-08-02T19:26:09Z","timestamp":1659468369000},"page":"1567-1575","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["The pathogenesis of cryptoglandular anal fistula: New insight into the immunological profile"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1415-621X","authenticated-orcid":false,"given":"Francesco","family":"Litta","sequence":"first","affiliation":[{"name":"Proctology Unit Fondazione Policlinico Universitario A. Gemelli IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1229-9671","authenticated-orcid":false,"given":"Andrea","family":"Papait","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze della Vita e Sanit\u00e0 Pubblica Universit\u00e0 Cattolica del Sacro Cuore  Rome Italy"},{"name":"Fondazione Policlinico Universitario \u2018Agostino Gemelli\u2019 IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donatella","family":"Lucchetti","sequence":"additional","affiliation":[{"name":"Dipartimento Universitario di Medicina e Chirurgia Traslazionale Universit\u00e0 Cattolica del Sacro Cuore  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6381-830X","authenticated-orcid":false,"given":"Serafina","family":"Farigu","sequence":"additional","affiliation":[{"name":"Centro di Ricerca E. Menni Fondazione Poliambulanza  Brescia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5092-9158","authenticated-orcid":false,"given":"Angelo","family":"Parello","sequence":"additional","affiliation":[{"name":"Proctology Unit Fondazione Policlinico Universitario A. Gemelli IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio Ricciardi","family":"Tenore","sequence":"additional","affiliation":[{"name":"Dipartimento Universitario di Medicina e Chirurgia Traslazionale Universit\u00e0 Cattolica del Sacro Cuore  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Campenn\u00ec","sequence":"additional","affiliation":[{"name":"Proctology Unit Fondazione Policlinico Universitario A. Gemelli IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonietta Rosa","family":"Silini","sequence":"additional","affiliation":[{"name":"Centro di Ricerca E. Menni Fondazione Poliambulanza  Brescia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Cristina","family":"Giustiniani","sequence":"additional","affiliation":[{"name":"UOC di Anatomia Patologica Fondazione Policlinico Universitario A. Gemelli IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ornella","family":"Parolini","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze della Vita e Sanit\u00e0 Pubblica Universit\u00e0 Cattolica del Sacro Cuore  Rome Italy"},{"name":"Fondazione Policlinico Universitario \u2018Agostino Gemelli\u2019 IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Sgambato","sequence":"additional","affiliation":[{"name":"Dipartimento Universitario di Medicina e Chirurgia Traslazionale Universit\u00e0 Cattolica del Sacro Cuore  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0556-0037","authenticated-orcid":false,"given":"Carlo","family":"Ratto","sequence":"additional","affiliation":[{"name":"Proctology Unit Fondazione Policlinico Universitario A. Gemelli IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,8,16]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.2147\/CEG.S198796"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v17.i28.3286"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00384-014-2091-8"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/bjs.7341"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1318.2009.01880.x"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10151-011-0803-4"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00384-006-0121-x"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/codi.12810"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/codi.13527"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10151-017-1645-5"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/ans.14874"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10151-016-1494-7"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/1512969"},{"key":"e_1_2_14_15_1","doi-asserted-by":"publisher","DOI":"10.14309\/ajg.0000000000001122"},{"key":"e_1_2_14_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02050307"},{"key":"e_1_2_14_17_1","doi-asserted-by":"publisher","DOI":"10.1148\/rg.321115040"},{"key":"e_1_2_14_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0053414"},{"key":"e_1_2_14_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.700009"},{"key":"e_1_2_14_20_1","doi-asserted-by":"publisher","DOI":"10.3109\/08830185.2014.954698"},{"key":"e_1_2_14_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-009-9345-1"},{"key":"e_1_2_14_22_1","doi-asserted-by":"publisher","DOI":"10.1080\/00365520701320489"},{"key":"e_1_2_14_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2012.09.012"},{"key":"e_1_2_14_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/codi.12991"},{"key":"e_1_2_14_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2008.04.017"},{"key":"e_1_2_14_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2017.50"},{"key":"e_1_2_14_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.07.010"},{"key":"e_1_2_14_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00005-014-0293-y"},{"key":"e_1_2_14_29_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0900368"},{"key":"e_1_2_14_30_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0801814"},{"key":"e_1_2_14_31_1","doi-asserted-by":"publisher","DOI":"10.1189\/JLB.0109046"},{"key":"e_1_2_14_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2010.05.004"},{"key":"e_1_2_14_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-43311-6"},{"key":"e_1_2_14_34_1","doi-asserted-by":"publisher","DOI":"10.1097\/MIB.0000000000000848"},{"key":"e_1_2_14_35_1","doi-asserted-by":"publisher","DOI":"10.4291\/wjgp.v10.i4.42"},{"key":"e_1_2_14_36_1","first-page":"2269","article-title":"Unique CD14 intestinal macrophages contribute to the pathogenesis of Crohn disease via IL\u201023\/IFN\u2010gamma axis","volume":"118","author":"Kamada N","year":"2008","journal-title":"J Clin Invest"},{"key":"e_1_2_14_37_1","first-page":"153","article-title":"Adalimumab treatment in Crohn's disease: an overview of long\u2010term efficacy and safety in light of the EXTEND trial","volume":"6","author":"Asgharpour A","year":"2013","journal-title":"Clin Exp Gastroenterol"},{"key":"e_1_2_14_38_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20090849"},{"key":"e_1_2_14_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-020-05422-6"},{"key":"e_1_2_14_40_1","doi-asserted-by":"publisher","DOI":"10.12659\/MSM.923287"},{"key":"e_1_2_14_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2021.04.017"},{"key":"e_1_2_14_42_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00510"},{"key":"e_1_2_14_43_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0087680"},{"key":"e_1_2_14_44_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20070075"}],"container-title":["Colorectal Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/codi.16290","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/codi.16290","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/codi.16290","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,20]],"date-time":"2023-08-20T02:02:24Z","timestamp":1692496944000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/codi.16290"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,16]]},"references-count":43,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2022,12]]}},"alternative-id":["10.1111\/codi.16290"],"URL":"https:\/\/doi.org\/10.1111\/codi.16290","archive":["Portico"],"relation":{},"ISSN":["1462-8910","1463-1318"],"issn-type":[{"value":"1462-8910","type":"print"},{"value":"1463-1318","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,16]]},"assertion":[{"value":"2022-06-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-07-27","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-08-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}