{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T20:08:33Z","timestamp":1791144513394,"version":"4.1.0"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2014,9,28]],"date-time":"2014-09-28T00:00:00Z","timestamp":1411862400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,3,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>\u2003<\/jats:title>\n                    <jats:p>Inflammatory bone resorption is a hallmark of periodontitis, and Tregs and Th2 cells are independently associated with disease progression attenuation. In this study, we employed an infection-triggered inflammatory osteolysis model to investigate the mechanisms underlying Treg and Th2 cell migration and the impact on disease outcome. Aggregatibacter actinomycetemcomitans\u2013infected C57Bl\/6 (wild-type [WT]) mice develop an intense inflammatory reaction and alveolar bone resorption, and Treg and Th2 cell migration is temporally associated with disease progression attenuation. Tregs extracted from the lesions preferentially express CCR4 and CCR8, whereas Th2 cells express CCR3, CCR4, and CCR8. The absence of CCR5 and CCR8 did not significantly impact the migration of Tregs and Th2 cells or affect the disease outcome. CCR4KO mice presented a minor reduction in Th2 cells in parallel with major impairment of Treg migration, which was associated with increased inflammatory bone loss and higher proinflammatory and osteoclastogenic cytokine levels. The blockade of the CCR4 ligand CCL22 in WT mice resulted in an increased inflammatory bone loss phenotype similar to that in the CCR4KO strain. Adoptive transfer of CCR4+ Tregs to the CCR4KO strain revert the increased disease phenotype to WT mice\u2013like levels; also, the in situ production of CCL22 in the lesions is mandatory for Tregs migration and the consequent bone loss arrest. The local release of exogenous CCL22 provided by poly(lactic-co-glycolic acid) (PLGA) microparticles promotes migration of Tregs and disease arrest in the absence of endogenous CCL22 in the IL-4KO strain, characterized by the lack of endogenous CCL22 production, defective migration of Tregs, and exacerbated bone loss. In summary, our results show that the IL-4\/CCL22\/CCR4 axis is involved in the migration of Tregs to osteolytic lesion sites, and attenuates development of lesions by inhibiting inflammatory migration and the production of proinflammatory and osteoclastogenic mediators. \u00a9 2014 American Society for Bone and Mineral Research<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jbmr.2376","type":"journal-article","created":{"date-parts":[[2014,9,28]],"date-time":"2014-09-28T23:24:22Z","timestamp":1411946662000},"page":"412-422","source":"Crossref","is-referenced-by-count":105,"title":["IL-4\/CCL22\/CCR4 Axis Controls Regulatory T-Cell Migration That Suppresses Inflammatory Bone Loss in Murine Experimental Periodontitis"],"prefix":"10.1093","volume":"30","author":[{"given":"Ana Claudia","family":"Araujo-Pires","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, School of Dentistry of BauruSao Paulo University (FOB\/USP)BauruSPBrazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreia Espindola","family":"Vieira","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, School of Dentistry of BauruSao Paulo University (FOB\/USP)BauruSPBrazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina Favaro","family":"Francisconi","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, School of Dentistry of BauruSao Paulo University (FOB\/USP)BauruSPBrazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia Cristina","family":"Biguetti","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, School of Dentistry of BauruSao Paulo University (FOB\/USP)BauruSPBrazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Glowacki","sequence":"additional","affiliation":[{"name":"The Center for Craniofacial RegenerationUniversity of PittsburghPittsburghPAUSA"},{"name":"The McGowan Institute for Regenerative MedicineUniversity of PittsburghPittsburghPAUSA"},{"name":"Department of Chemical EngineeringUniversity of PittsburghPittsburghPAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sayuri","family":"Yoshizawa","sequence":"additional","affiliation":[{"name":"Department of Oral BiologyUniversity of PittsburghPittsburghPAUSA"},{"name":"The Center for Craniofacial RegenerationUniversity of PittsburghPittsburghPAUSA"},{"name":"The McGowan Institute for Regenerative MedicineUniversity of PittsburghPittsburghPAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Paula","family":"Campanelli","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, School of Dentistry of BauruSao Paulo University (FOB\/USP)BauruSPBrazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Paula Favaro","family":"Trombone","sequence":"additional","affiliation":[{"name":"Department of Biological and Health SciencesSacred Heart University (USC)BauruSPBrazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles S","family":"Sfeir","sequence":"additional","affiliation":[{"name":"Department of BioengineeringUniversity of PittsburghPittsburghPAUSA"},{"name":"Department of Oral BiologyUniversity of PittsburghPittsburghPAUSA"},{"name":"The Center for Craniofacial RegenerationUniversity of PittsburghPittsburghPAUSA"},{"name":"The McGowan Institute for Regenerative MedicineUniversity of PittsburghPittsburghPAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven R","family":"Little","sequence":"additional","affiliation":[{"name":"Department of ImmunologyUniversity of PittsburghPittsburghPAUSA"},{"name":"Department of BioengineeringUniversity of PittsburghPittsburghPAUSA"},{"name":"The Center for Craniofacial RegenerationUniversity of PittsburghPittsburghPAUSA"},{"name":"The McGowan Institute for Regenerative MedicineUniversity of PittsburghPittsburghPAUSA"},{"name":"Department of Chemical EngineeringUniversity of PittsburghPittsburghPAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo Pompermaier","family":"Garlet","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, School of Dentistry of BauruSao Paulo University (FOB\/USP)BauruSPBrazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,9,28]]},"reference":[{"key":"2024020319184745900_jbmr2376-bib-0001","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1111\/j.1600-051X.2005.00822.x","article-title":"European Workshop in Periodontology Group C. 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