{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:59:30Z","timestamp":1790794770201,"version":"4.1.0"},"reference-count":77,"publisher":"Begell House","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Crit Rev Immunol"],"published-print":{"date-parts":[[2026]]},"abstract":"

Current therapeutic strategies for inflammatory bowel disease often rely on systemic immunosuppression or single-target biologics, which can lead to significant side effects or incomplete remission. To overcome this therapeutic hurdle, we recently proposed engineering dendritic cells (DCs) to <i>de novo<\/i> synthesize high concentrations of the active vitamin D (1,25&#91;OH&#93;<sub>2<\/sub>D) and A (retinoic acid or RA) because 1,25(OH)<sub>2<\/sub>D directly stimulates the expression of Foxp3 (the master regulator of CD4<sup>&#43;<\/sup> Tregs) and RA induces gut-homing receptor expression. In our previous studies, we engineered mouse DCs using a lentiviral vector to overexpress CYP27B1 (encoding 1&alpha;-hydroxylase) and ALDH1A2 (encoding RALDH2) to synthesize 1,25(OH)<sub>2<\/sub>D and RA, respectively. The engineered DCs stimulated CD4<sup>&#43;<\/sup>Foxp3<sup>&#43;<\/sup> Tregs expressing CCR9 (a gut-homing receptor) both <i>in vitro<\/i> and <i>in vivo<\/i>. In addition, the engineered DCs robustly suppressed experimental colitis, a process that depended on CD4<sup>&#43;<\/sup>Foxp3<sup>&#43;<\/sup> Tregs. In addition, the engineered DCs did not cause hypercalcemia, the major side effect associated with systemically high 1,25(OH)<sub>2<\/sub>D concentrations, suggesting a safety profile. Moreover, the engineered DCs upregulated tissue expression of CYP27B1 and ALDH1A2 genes for thirty days of the observational period. To evaluate the potential clinical translation of the engineered DCs, this study extended our previous animal studies to humans. Our data demonstrated that engineered human DCs, like their mouse counterparts, stimulated CCR9<sup>&#43;<\/sup>CD4<sup>&#43;<\/sup>Foxp3<sup>&#43;<\/sup> Tregs. Notably, our human data revealed that the engineered human DCs also stimulated &alpha;4&beta;7<sup>&#43;<\/sup> and &alpha;4&beta;7<sup>&#43;<\/sup>CCR9<sup>&#43;<\/sup> CD4<sup>&#43;<\/sup>Foxp3<sup>&#43;<\/sup> Tregs, a finding validated <i>in vivo<\/i> in mice. This finding is clinically significant because CCR9 mediates homing to the small intestine, while a4b7 targets both the small and large intestines, thereby offering \"pan-intestinal\" therapeutic coverage. Our human data thus further support the engineered DCs as a promising therapy for inflammatory bowel disease. Additionally, because CCR9 is a homing receptor for inflammation, the engineered DCs can potentially be a solution for a broad range of inflammatory diseases.<\/p>","DOI":"10.1615\/critrevimmunol.2026062974","type":"journal-article","created":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T19:12:08Z","timestamp":1778267528000},"page":"53-74","source":"Crossref","is-referenced-by-count":0,"title":["Engineered Dendritic Cells Imprint Dual Gut-Homing Specificity on Human Tregs for Pan-Intestinal Immunotolerance"],"prefix":"10.1615","volume":"46","author":[{"given":"Nisar Ali","family":"Shaikh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Bing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Baylink","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolei","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"613","reference":[{"key":"1","unstructured":"US Center for Disease Control and Prevention (CDC). Inflammatory bowel disease (IBD) [Internet]. 2024 [cited November 14, 2025]. Available from: https:\/\/www.cdc.gov\/inflammatory-bowel-disease\/php\/facts-stats\/index.html."},{"key":"2","doi-asserted-by":"crossref","unstructured":"Abraham C, Cho JH. Inflammatory bowel disease. N Engl J Med. 2009;361(21):2066\u201378. PubMed PMID: 19923578. PMCID: PMC3491806. Epub 2009\/11\/20.","DOI":"10.1056\/NEJMra0804647"},{"key":"3","doi-asserted-by":"crossref","unstructured":"Kaser A, Zeissig S, Blumberg RS. Inflammatory bowel disease. Annu Rev Immunol. 2010;28:573\u2013621. PubMed PMID: 20192811. Epub 2010\/03\/03. eng.","DOI":"10.1146\/annurev-immunol-030409-101225"},{"key":"4","doi-asserted-by":"crossref","unstructured":"Reinglas J, Gonczi L, Kurt Z, Bessissow T, Lakatos PL. Positioning of old and new biologicals and small molecules in the treatment of inflammatory bowel diseases. World J Gastroenterol. 2018;24(32):3567\u201382. PubMed PMID: 30166855. PMCID: 6113721. Epub 2018\/09\/01. eng.","DOI":"10.3748\/wjg.v24.i32.3567"},{"key":"5","unstructured":"Paramsothy S, Rosenstein AK, Mehandru S, Colombel JF. The current state of the art for biological therapies and new small molecules in inflammatory bowel disease. Mucosal Immunol. 2018. PubMed PMID: 29907872. Epub 2018\/06\/17. eng."},{"key":"6","doi-asserted-by":"crossref","unstructured":"Clifford DB, De Luca A, Simpson DM, Arendt G, Giovannoni G, Nath A. Natalizumab-associated progressive multifocal leukoencephalopathy in patients with multiple sclerosis: Lessons from 28 cases. Lancet Neurol. 2010;9(4):438\u201346. PubMed PMID: 20298967. Epub 2010\/03\/20. eng.","DOI":"10.1016\/S1474-4422(10)70028-4"},{"key":"7","doi-asserted-by":"crossref","unstructured":"Kishore J, Ghoshal U, Ghoshal UC, Krishnani N, Kumar S, Singh M, Ayyagari A. Infection with cytomegalovirus in patients with inflammatory bowel disease: Prevalence, clinical significance and outcome. J Med Microbiol. 2004;53(Pt 11):1155\u201360. PubMed PMID: 15496396. Epub 2004\/10\/22.","DOI":"10.1099\/jmm.0.45629-0"},{"key":"8","doi-asserted-by":"crossref","unstructured":"Stamatiades GA, Ioannou P, Petrikkos G, Tsioutis C. Fungal infections in patients with inflammatory bowel disease: A systematic review. Mycoses. 2018;61(6):366\u201376. PubMed PMID: 29453860. PMCID: PMC5980782. Epub 2018\/02\/18.","DOI":"10.1111\/myc.12753"},{"key":"9","doi-asserted-by":"crossref","unstructured":"Rao K, Higgins PD. Epidemiology, diagnosis, and management of clostridium difficile infection in patients with inflammatory bowel disease. Inflamm Bowel Dis. 2016;22(7):1744\u201354. PubMed PMID: 27120571. PMCID: PMC4911291. Epub 2016\/04\/28.","DOI":"10.1097\/MIB.0000000000000793"},{"key":"10","doi-asserted-by":"crossref","unstructured":"Wewer MD, Letnar G, Andersen KK, Malham M, Wewer V, Seidelin JB, Bendtsen F, Burisch J. Thiopurines and the risk of cancer in patients with inflammatory bowel disease and reference individuals without inflammatory bowel disease: A Danish Nationwide Cohort Study (1996-2018). Clin Gastroenterol Hepatol. 2025;23(6):1030\u20138. PubMed PMID: 39209201. Epub 20240828.","DOI":"10.1016\/j.cgh.2024.08.006"},{"key":"11","doi-asserted-by":"crossref","unstructured":"Peyrin-Biroulet L, Danese S, Argollo M, Pouillon L, Peppas S, Gonzalez-Lorenzo M, Lytras T, Bonovas S. Loss of response to vedolizumab and ability of dose intensification to restore response in patients with Crohn\u2019s disease or ulcerative colitis: A systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2019;17(5):838\u201346 e2. PubMed PMID: 29935327. Epub 2018\/06\/24.","DOI":"10.1016\/j.cgh.2018.06.026"},{"key":"12","doi-asserted-by":"crossref","unstructured":"Lee HW, Yoon SY, Singh TD, Choi YJ, Lee HJ, Park JY, Jeong SY, Lee SW, Ha JH, Ahn BC, Jeon YH, Lee J. Tracking of dendritic cell migration into lymph nodes using molecular imaging with sodium iodide symporter and enhanced firefly luciferase genes. Sci Rep. 2015;5:9865. PubMed PMID: 25974752. PMCID: 4431315. Epub 2015\/05\/15. eng.","DOI":"10.1038\/srep09865"},{"key":"13","doi-asserted-by":"crossref","unstructured":"MartIn-Fontecha A, Sebastiani S, Hopken UE, Uguccioni M, Lipp M, Lanzavecchia A, Sallusto F. Regulation of dendritic cell migration to the draining lymph node: Impact on T lymphocyte traffic and priming. J Exp Med. 2003;198(4):615\u201321. PubMed PMID: 12925677. PMCID: 2194169. Epub 2003\/08\/20. eng.","DOI":"10.1084\/jem.20030448"},{"key":"14","doi-asserted-by":"crossref","unstructured":"Randolph GJ, Angeli V, Swartz MA. Dendritic-cell trafficking to lymph nodes through lymphatic vessels. Nat Rev Immunol. 2005;5(8):617\u201328. PubMed PMID: 16056255. Epub 2005\/08\/02. eng.","DOI":"10.1038\/nri1670"},{"key":"15","doi-asserted-by":"crossref","unstructured":"Kang SW, Kim SH, Lee N, Lee WW, Hwang KA, Shin MS, Lee SH, Kim WU, Kang I. 1,25-Dihyroxyvitamin D3 promotes FOXP3 expression via binding to vitamin D response elements in its conserved noncoding sequence region. J Immunol. 2012;188(11):5276\u201382. PubMed PMID: 22529297. PMCID: 3358577. Epub 2012\/04\/25. eng.","DOI":"10.4049\/jimmunol.1101211"},{"key":"16","doi-asserted-by":"crossref","unstructured":"Iwata M, Hirakiyama A, Eshima Y, Kagechika H, Kato C, Song SY. Retinoic acid imprints gut-homing specificity on T cells. Immunity. 2004;21(4):527\u201338. PubMed PMID: 15485630. Epub 2004\/10\/16. eng.","DOI":"10.1016\/j.immuni.2004.08.011"},{"key":"17","doi-asserted-by":"crossref","unstructured":"Zeng R, Oderup C, Yuan R, Lee M, Habtezion A, Hadeiba H, Butcher EC. Retinoic acid regulates the development of a gut-homing precursor for intestinal dendritic cells. Mucosal Immunol. 2013;6(4):847\u201356. PubMed PMID: 23235743. PMCID: PMC3612556. Epub 20121212.","DOI":"10.1038\/mi.2012.123"},{"key":"18","unstructured":"Smith DC, Johnson CS, Freeman CC, Muindi J, Wilson JW, Trump DL. A Phase I trial of calcitriol (1,25-dihydroxycholecalciferol) in patients with advanced malignancy. Clin Cancer Res. 1999;5(6):1339\u201345. PubMed PMID: 10389917. Epub 1999\/07\/02. eng."},{"key":"19","doi-asserted-by":"crossref","unstructured":"Hausler D, Torke S, Peelen E, Bertsch T, Djukic M, Nau R, Larochelle C, Zamvil SS, Bruck W, Weber MS. High dose vitamin D exacerbates central nervous system autoimmunity by raising T-cell excitatory calcium. Brain. 2019;142(9):2737\u201355. PubMed PMID: 31302671. PMCID: PMC6736324. Epub 2019\/07\/16.","DOI":"10.1093\/brain\/awz190"},{"key":"20","doi-asserted-by":"crossref","unstructured":"Hygum K, Wulff CN, Harslof T, Boysen AK, Rossen PB, Langdahl BL, Safwat AA. Hypercalcemia in metastatic GIST caused by systemic elevated calcitriol: A case report and review of the literature. BMC Cancer. 2015;15:788. PubMed PMID: 26499069. PMCID: PMC4619287. Epub 20151024.","DOI":"10.1186\/s12885-015-1823-7"},{"key":"21","doi-asserted-by":"crossref","unstructured":"Asonitis N, Angelousi A, Zafeiris C, Lambrou GI, Dontas I, Kassi E. Diagnosis, pathophysiology and management of hypercalcemia in malignancy: A review of the literature. Horm Metab Res. 2019;51(12):770\u20138. PubMed PMID: 31826272. Epub 20191211.","DOI":"10.1055\/a-1049-0647"},{"key":"22","doi-asserted-by":"crossref","unstructured":"Probert C. Commentary: Vitamin D supplementation in Crohn\u2019s disease. Aliment Pharmacol Ther. 2020;51(1):201\u20132. PubMed PMID: 31850585. Epub 2019\/12\/19.","DOI":"10.1111\/apt.15524"},{"key":"23","unstructured":"Guzman-Prado Y, Samson O, Segal JP, Limdi JK, Hayee B. Vitamin D therapy in adults with inflammatory bowel disease: A systematic review and meta-analysis. Inflamm Bowel Dis. 2020. PubMed PMID: 32385487. Epub 2020\/05\/10."},{"key":"24","doi-asserted-by":"crossref","unstructured":"Borgan SM, Khan LZ, Makin V. Hypercalcemia and vitamin A: A vitamin to keep in mind. Cleve Clin J Med. 2022;89(2):99\u2013105. PubMed PMID: 35105698. Epub 20220201.","DOI":"10.3949\/ccjm.89a.21056"},{"key":"25","doi-asserted-by":"crossref","unstructured":"Penniston KL, Tanumihardjo SA. The acute and chronic toxic effects of vitamin A. Am J Clin Nutr. 2006;83(2):191\u2013201. PubMed PMID: 16469975. Epub 2006\/02\/14. eng.","DOI":"10.1093\/ajcn\/83.2.191"},{"key":"26","unstructured":"Muindi JR, Young CW, Warrell RP, Jr. Clinical pharmacology of all-trans retinoic acid. Leukemia. 1994;8(Suppl 3):S16\u201321. PubMed PMID: 7808019."},{"key":"27","doi-asserted-by":"crossref","unstructured":"Ferguson SA, Siitonen PH, Cisneros FJ, Gough B, Young JF. Steady state pharmacokinetics of oral treatment with 13-cis-retinoic acid or all-trans-retinoic acid in male and female adult rats. Basic Clin Pharmacol Toxicol. 2006;98(6):582\u20137. PubMed PMID: 16700821.","DOI":"10.1111\/j.1742-7843.2006.pto_359.x"},{"key":"28","doi-asserted-by":"crossref","unstructured":"Lips P. Relative value of 25(OH)D and 1,25(OH)2D measurements. J Bone Miner Res. 2007;22(11):1668\u201371. PubMed PMID: 17645404. Epub 2007\/07\/25.","DOI":"10.1359\/jbmr.070716"},{"key":"29","doi-asserted-by":"crossref","unstructured":"Datta P, Philipsen PA, Olsen P, Bogh MK, Johansen P, Schmedes AV, Morling N, Wulf HC. The half-life of 25(OH)D after UVB exposure depends on gender and vitamin D receptor polymorphism but mainly on the start level. Photochem Photobiol Sci. 2017;16(6):985\u201395. PubMed PMID: 28485745. Epub 2017\/05\/10.","DOI":"10.1039\/c6pp00258g"},{"key":"30","doi-asserted-by":"crossref","unstructured":"Xu Y, Cheng Y, Baylink DJ, Wasnik S, Goel G, Huang M, Cao H, Qin X, Lau KW, Chan C, Koch A, Pham LH, Zhang J, Li CH, Wang X, Berumen EC, Smith J, Tang X. In vivo generation of gut-homing regulatory T cells for the suppression of colitis. J Immunol. 2019;202(12):3447\u201357. PubMed PMID: 31053627. Epub 2019\/05\/06. eng.","DOI":"10.4049\/jimmunol.1800018"},{"key":"31","doi-asserted-by":"crossref","unstructured":"Dzutsev A, Hogg A, Sui Y, Solaymani-Mohammadi S, Yu H, Frey B, Wang Y, Berzofsky JA. Differential T cell homing to colon vs. small intestine is imprinted by local CD11c(+) APCs that determine homing receptors. J Leukoc Biol. 2017;102(6):1381\u20138. PubMed PMID: 28951425. PMCID: PMC5669635. Epub 20170926.","DOI":"10.1189\/jlb.1A1116-463RR"},{"key":"32","doi-asserted-by":"crossref","unstructured":"Wang C, Kang SG, HogenEsch H, Love PE, Kim CH. Retinoic acid determines the precise tissue tropism of inflammatory Th17 cells in the intestine. J Immunol. 2010;184(10):5519\u201326. PubMed PMID: 20400707. PMCID: PMC3009589. Epub 20100416.","DOI":"10.4049\/jimmunol.0903942"},{"key":"33","doi-asserted-by":"crossref","unstructured":"Dull T, Zufferey R, Kelly M, Mandel RJ, Nguyen M, Trono D, Naldini L. A third-generation lentivirus vector with a conditional packaging system. J Virol. 1998;72(11):8463\u201371.","DOI":"10.1128\/JVI.72.11.8463-8471.1998"},{"key":"34","doi-asserted-by":"crossref","unstructured":"Xu Y, Baylink DJ, Cao H, Xiao J, Abdalla MI, Wasnik S, Tang X. Inflammation- and gut-homing macrophages, engineered to de novo overexpress active vitamin d, promoted the regenerative function of intestinal stem cells. Int J Mol Sci. 2021;22(17):9516.","DOI":"10.3390\/ijms22179516"},{"key":"35","unstructured":"Boyum A. Isolation of mononuclear cells and granulocytes from human blood. Isolation of monuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedimentation at 1 g. Scand J Clin Lab Invest Suppl. 1968;97:77\u201389. PubMed PMID: 4179068."},{"key":"36","doi-asserted-by":"crossref","unstructured":"Xu W, Watts DM, Costanzo MC, Tang X, Venegas LA, Jiao F, Sette A, Sidney J, Sewell AK, Wooldridge L, Makino S, Morrill JC, Peters CJ, Kan-Mitchell J. The nucleocapsid protein of Rift Valley fever virus is a potent human CD8+ T cell antigen and elicits memory responses. PLoS One. 2013;8(3):e59210. PubMed PMID: 23527138. PMCID: PMC3601065. Epub 2013\/03\/26.","DOI":"10.1371\/journal.pone.0059210"},{"key":"37","doi-asserted-by":"crossref","unstructured":"Sallusto F, Schaerli P, Loetscher P, Schaniel C, Lenig D, Mackay CR, Qin S, Lanzavecchia A. Rapid and coordinated switch in chemokine receptor expression during dendritic cell maturation. Eur J Immunol. 1998;28(9):2760\u20139. PubMed PMID: 9754563.","DOI":"10.1002\/(SICI)1521-4141(199809)28:09<2760::AID-IMMU2760>3.0.CO;2-N"},{"key":"38","doi-asserted-by":"crossref","unstructured":"Shaikh NA, Zhang XB, Abdalla MI, Baylink DJ, Tang X. Enhancing human Treg cell induction through engineered dendritic cells and zinc supplementation. Crit Rev Immunol. 2024;44(3):37\u201352. PubMed PMID: 38421704. PMCID: PMC11015935.","DOI":"10.1615\/CritRevImmunol.2023050325"},{"key":"39","doi-asserted-by":"crossref","unstructured":"Mora JR, Iwata M, Eksteen B, Song SY, Junt T, Senman B, Otipoby KL, Yokota A, Takeuchi H, Ricciardi-Castagnoli P, Rajewsky K, Adams DH, von Andrian UH. Generation of gut-homing IgA-secreting B cells by intestinal dendritic cells. Science. 2006;314(5802):1157\u201360. PubMed PMID: 17110582.","DOI":"10.1126\/science.1132742"},{"key":"40","doi-asserted-by":"crossref","unstructured":"Mora JR, Bono MR, Manjunath N, Weninger W, Cavanagh LL, Rosemblatt M, Von Andrian UH. Selective imprinting of gut-homing T cells by Peyer\u2019s patch dendritic cells. Nature. 2003;424(6944):88\u201393. PubMed PMID: 12840763.","DOI":"10.1038\/nature01726"},{"key":"41","doi-asserted-by":"crossref","unstructured":"Iwata M, Yokota A. Retinoic acid production by intestinal dendritic cells. Vitam Horm. 2011;86:127\u201352. PubMed PMID: 21419270. Epub 2011\/03\/23. eng.","DOI":"10.1016\/B978-0-12-386960-9.00006-X"},{"key":"42","doi-asserted-by":"crossref","unstructured":"Holick MF. Vitamin D deficiency in 2010: Health benefits of vitamin D and sunlight: A D-bate. Nat Rev Endocrinol. 2011;7(2):73\u20135. PubMed PMID: 21263437.","DOI":"10.1038\/nrendo.2010.234"},{"key":"43","doi-asserted-by":"crossref","unstructured":"Holick MF. The vitamin D deficiency pandemic: Approaches for diagnosis, treatment and prevention. Rev Endocr Metab Disord. 2017;18(2):153\u201365. PubMed PMID: 28516265. Epub 2017\/05\/19. eng.","DOI":"10.1007\/s11154-017-9424-1"},{"key":"44","doi-asserted-by":"crossref","unstructured":"Hewison M, Freeman L, Hughes SV, Evans KN, Bland R, Eliopoulos AG, Kilby MD, Moss PA, Chakraverty R. Differential regulation of vitamin D receptor and its ligand in human monocyte-derived dendritic cells. J Immunol. 2003;170(11):5382\u201390. PubMed PMID: 12759412. Epub 2003\/05\/22.","DOI":"10.4049\/jimmunol.170.11.5382"},{"key":"45","doi-asserted-by":"crossref","unstructured":"Fritsche J, Mondal K, Ehrnsperger A, Andreesen R, Kreutz M. Regulation of 25-hydroxyvitamin D3-1 alpha-hydroxylase and production of 1 alpha,25-dihydroxyvitamin D3 by human dendritic cells. Blood. 2003;102(9):3314\u20136. PubMed PMID: 12855575. Epub 2003\/07\/12.","DOI":"10.1182\/blood-2002-11-3521"},{"key":"46","doi-asserted-by":"crossref","unstructured":"Molenaar R, Knippenberg M, Goverse G, Olivier BJ, de Vos AF, O\u2019Toole T, Mebius RE. Expression of retinaldehyde dehydrogenase enzymes in mucosal dendritic cells and gut-draining lymph node stromal cells is controlled by dietary vitamin A. J Immunol. 2011;186(4):1934\u201342. PubMed PMID: 21220692. Epub 20110110.","DOI":"10.4049\/jimmunol.1001672"},{"key":"47","doi-asserted-by":"crossref","unstructured":"Yokota A, Takeuchi H, Maeda N, Ohoka Y, Kato C, Song SY, Iwata M. GM-CSF and IL-4 synergistically trigger dendritic cells to acquire retinoic acid-producing capacity. Int Immunol. 2009;21(4):361\u201377. PubMed PMID: 19190084. PMCID: PMC2660862. Epub 20090203.","DOI":"10.1093\/intimm\/dxp003"},{"key":"48","doi-asserted-by":"crossref","unstructured":"Elgueta R, Sepulveda FE, Vilches F, Vargas L, Mora JR, Bono MR, Rosemblatt M. Imprinting of CCR9 on CD4 T cells requires IL-4 signaling on mesenteric lymph node dendritic cells. J Immunol. 2008;180(10):6501\u20137. PubMed PMID: 18453568.","DOI":"10.4049\/jimmunol.180.10.6501"},{"key":"49","doi-asserted-by":"crossref","unstructured":"Manicassamy S, Ravindran R, Deng J, Oluoch H, Denning TL, Kasturi SP, Rosenthal KM, Evavold BD, Pulendran B. Toll-like receptor 2-dependent induction of vitamin A-metabolizing enzymes in dendritic cells promotes T regulatory responses and inhibits autoimmunity. Nat Med. 2009;15(4):401\u20139. PubMed PMID: 19252500. PMCID: PMC2768543. Epub 20090301.","DOI":"10.1038\/nm.1925"},{"key":"50","doi-asserted-by":"crossref","unstructured":"Uematsu S, Fujimoto K, Jang MH, Yang BG, Jung YJ, Nishiyama M, Sato S, Tsujimura T, Yamamoto M, Yokota Y, Kiyono H, Miyasaka M, Ishii KJ, Akira S. Regulation of humoral and cellular gut immunity by lamina propria dendritic cells expressing Toll-like receptor 5. Nat Immunol. 2008;9(7):769\u201376. PubMed PMID: 18516037. Epub 20080530.","DOI":"10.1038\/ni.1622"},{"key":"51","doi-asserted-by":"crossref","unstructured":"Wang S, Villablanca EJ, De Calisto J, Gomes DC, Nguyen DD, Mizoguchi E, Kagan JC, Reinecker HC, Hacohen N, Nagler C, Xavier RJ, Rossi-Bergmann B, Chen YB, Blomhoff R, Snapper SB, Mora JR. MyD88-dependent TLR1\/2 signals educate dendritic cells with gut-specific imprinting properties. J Immunol. 2011;187(1):141\u201350. PubMed PMID: 21646294. PMCID: PMC3119749. Epub 20110606.","DOI":"10.4049\/jimmunol.1003740"},{"key":"52","doi-asserted-by":"crossref","unstructured":"Villablanca EJ, Wang S, de Calisto J, Gomes DC, Kane MA, Napoli JL, Blaner WS, Kagechika H, Blomhoff R, Rosemblatt M, Bono MR, von Andrian UH, Mora JR. MyD88 and retinoic acid signaling pathways interact to modulate gastrointestinal activities of dendritic cells. Gastroenterology. 2011;141(1):176\u201385. PubMed PMID: 21596042. PMCID: PMC3129445. Epub 20110416.","DOI":"10.1053\/j.gastro.2011.04.010"},{"key":"53","doi-asserted-by":"crossref","unstructured":"Sato T, Kitawaki T, Fujita H, Iwata M, Iyoda T, Inaba K, Ohteki T, Hasegawa S, Kawada K, Sakai Y, Ikeuchi H, Nakase H, Niwa A, Takaori-Kondo A, Kadowaki N. Human CD1c(+) myeloid dendritic cells acquire a high level of retinoic acid-producing capacity in response to vitamin D(3). J Immunol. 2013;191(6):3152\u201360. PubMed PMID: 23966631. Epub 20130821.","DOI":"10.4049\/jimmunol.1203517"},{"key":"54","doi-asserted-by":"crossref","unstructured":"Szatmari I, Pap A, Ruhl R, Ma JX, Illarionov PA, Besra GS, Rajnavolgyi E, Dezso B, Nagy L. PPARgamma controls CD1d expression by turning on retinoic acid synthesis in developing human dendritic cells. J Exp Med. 2006;203(10):2351\u201362. PubMed PMID: 16982809. PMCID: PMC2118109. Epub 20060918.","DOI":"10.1084\/jem.20060141"},{"key":"55","doi-asserted-by":"crossref","unstructured":"Li CH, Zhang J, Baylink DJ, Wang X, Goparaju NB, Xu Y, Wasnik S, Cheng Y, Berumen EC, Qin X, Lau KW, Tang X. Dendritic cells, engineered to overexpress 25-hydroxyvitamin D 1alpha-hydroxylase and pulsed with a myelin antigen, provide myelin-specific suppression of ongoing experimental allergic encephalomyelitis. FASEB J. 2017;31(7):2996. PubMed PMID: 28363955. Epub 2017\/04\/02. eng.","DOI":"10.1096\/fj.201601243R"},{"key":"56","doi-asserted-by":"crossref","unstructured":"Li B, Baylink DJ, Walter MH, Lau KH, Meng X, Wang J, Cherkas A, Tang X, Qin X. Targeted 25-hydroxyvitamin D3 1alpha-hydroxylase adoptive gene therapy ameliorates dss-induced colitis without causing hypercalcemia in mice. Mol Ther. 2015;23(2):339\u201351. PubMed PMID: 25327179. PMCID: 4445611. Epub 2014\/10\/21.eng.","DOI":"10.1038\/mt.2014.201"},{"key":"57","doi-asserted-by":"crossref","unstructured":"Shaikh NA, Liu C, Yin Y, Baylink DJ, Tang X. 1,25-Dihydroxyvitamin D enhances the regenerative function of Lgr5(+) intestinal stem cells in vitro and in vivo. Cells. 2024;13(17). PubMed PMID: 39273035. PMCID: PMC11394149. Epub 20240831.","DOI":"10.3390\/cells13171465"},{"key":"58","doi-asserted-by":"crossref","unstructured":"Meeker S, Seamons A, Maggio-Price L, Paik J. Protective links between vitamin D, inflammatory bowel disease and colon cancer. World J Gastroenterol. 2016;22(3):933\u201348. PubMed PMID: 26811638. PMCID: PMC4716046.","DOI":"10.3748\/wjg.v22.i3.933"},{"key":"59","doi-asserted-by":"crossref","unstructured":"Wasnik S, Sharma I, Baylink DJ, Tang X. Vitamin D as a potential therapy for multiple sclerosis: Where are we? Int J Mol Sci. 2020;21(9). PubMed PMID: 32354174. PMCID: PMC7247155. Epub 2020\/05\/02.","DOI":"10.3390\/ijms21093102"},{"key":"60","doi-asserted-by":"crossref","unstructured":"Feige J, Moser T, Bieler L, Schwenker K, Hauer L, Sellner J. Vitamin D supplementation in multiple sclerosis: A critical analysis of potentials and threats. Nutrients. 2020;12(3). PubMed PMID: 32188044. PMCID: PMC7146466. Epub 2020\/03\/20.","DOI":"10.3390\/nu12030783"},{"key":"61","doi-asserted-by":"crossref","unstructured":"Yu J, Sharma P, Girgis CM, Gunton JE. Vitamin D and beta cells in type 1 diabetes: A systematic review. Int J Mol Sci. 2022;23(22). PubMed PMID: 36430915. PMCID: PMC9696701. Epub 2022\/11\/27.","DOI":"10.3390\/ijms232214434"},{"key":"62","doi-asserted-by":"crossref","unstructured":"Tang X. Therapeutic applications of vitamin D. Front Biosci. 2025;30(4):37218. PubMed PMID: 40302351.","DOI":"10.31083\/FBL37218"},{"key":"63","doi-asserted-by":"crossref","unstructured":"Chen AC, Gudas LJ. An analysis of retinoic acid-induced gene expression and metabolism in AB1 embryonic stem cells. J Biol Chem. 1996;271(25):14971\u201380. PubMed PMID: 8663043.","DOI":"10.1074\/jbc.271.25.14971"},{"key":"64","doi-asserted-by":"crossref","unstructured":"Randolph RK, Simon M. Metabolism of all-trans-retinoic acid by cultured human epidermal keratinocytes. J Lipid Res. 1997;38(7):1374\u201383. PubMed PMID: 9254063.","DOI":"10.1016\/S0022-2275(20)37420-4"},{"key":"65","doi-asserted-by":"crossref","unstructured":"Sigmundsdottir H, Pan J, Debes GF, Alt C, Habtezion A, Soler D, Butcher EC. DCs metabolize sunlight-induced vitamin D3 to \u2018program\u2019 T cell attraction to the epidermal chemokine CCL27. Nat Immunol. 2007;8(3):285\u201393. PubMed PMID: 17259988. Epub 2007\/01\/30. eng.","DOI":"10.1038\/ni1433"},{"key":"66","doi-asserted-by":"crossref","unstructured":"Trivedi PJ, Bruns T, Ward S, Mai M, Schmidt C, Hirschfield GM, Weston CJ, Adams DH. Intestinal CCL25 expression is increased in colitis and correlates with inflammatory activity. J Autoimmun. 2016;68:98\u2013104. PubMed PMID: 26873648. PMCID: PMC4803021. Epub 2016\/02\/14.","DOI":"10.1016\/j.jaut.2016.01.001"},{"key":"67","doi-asserted-by":"crossref","unstructured":"Bekker P, Ebsworth K, Walters MJ, Berahovich RD, Ertl LS, Charvat TT, Punna S, Powers JP, Campbell JJ, Sullivan TJ, Jaen JC, Schall TJ. CCR9 antagonists in the treatment of ulcerative colitis. Mediators Inflamm. 2015;2015:628340. PubMed PMID: 26457007. PMCID: PMC4592714. Epub 20150920.","DOI":"10.1155\/2015\/628340"},{"key":"68","doi-asserted-by":"crossref","unstructured":"Igaki K, Komoike Y, Nakamura Y, Watanabe T, Yamasaki M, Fleming P, Yang L, Soler D, Fedyk E, Tsuchimori N. MLN3126, an antagonist of the chemokine receptor CCR9, ameliorates inflammation in a T cell mediated mouse colitis model. Int Immunopharmacol. 2018;60:160\u20139. PubMed PMID: 29730559. Epub 20180504.","DOI":"10.1016\/j.intimp.2018.04.049"},{"key":"69","doi-asserted-by":"crossref","unstructured":"Wermers JD, McNamee EN, Wurbel MA, Jedlicka P, Rivera-Nieves J. The chemokine receptor CCR9 is required for the T-cell-mediated regulation of chronic ileitis in mice. Gastroenterology. 2011;140(5):1526\u201335 e3. PubMed PMID: 21300065. PMCID: PMC3086928. Epub 20110204.","DOI":"10.1053\/j.gastro.2011.01.044"},{"key":"70","doi-asserted-by":"crossref","unstructured":"Nakamoto N, Ebinuma H, Kanai T, Chu PS, Ono Y, Mikami Y, Ojiro K, Lipp M, Love PE, Saito H, Hibi T. CCR9+ macrophages are required for acute liver inflammation in mouse models of hepatitis. Gastroenterology. 2012;142(2):366\u201376. PubMed PMID: 22079594. Epub 20111110.","DOI":"10.1053\/j.gastro.2011.10.039"},{"key":"71","doi-asserted-by":"crossref","unstructured":"Yokoyama W, Kohsaka H, Kaneko K, Walters M, Takayasu A, Fukuda S, Miyabe C, Miyabe Y, Love PE, Nakamoto N, Kanai T, Watanabe-Imai K, Charvat TT, Penfold ME, Jaen J, Schall TJ, Harigai M, Miyasaka N, Nanki T. Abrogation of CC chemokine receptor 9 ameliorates collagen-induced arthritis of mice. Arthritis Res Ther. 2014;16(5):445. PubMed PMID: 25248373. PMCID: PMC4201712. Epub 20140924.","DOI":"10.1186\/s13075-014-0445-9"},{"key":"72","doi-asserted-by":"crossref","unstructured":"Huang Y, Wang D, Wang X, Zhang Y, Liu T, Chen Y, Tang Y, Wang T, Hu D, Huang C. Abrogation of CC chemokine receptor 9 ameliorates ventricular remodeling in mice after myocardial infarction. Sci Rep. 2016;6:32660. PubMed PMID: 27585634. PMCID: PMC5009347. Epub 20160902.","DOI":"10.1038\/srep32660"},{"key":"73","doi-asserted-by":"crossref","unstructured":"Lopez-Pacheco C, Soldevila G, Du Pont G, Hernandez-Pando R, Garcia-Zepeda EA. CCR9 is a key regulator of early phases of allergic airway inflammation. Mediators Inflamm. 2016;2016:3635809. PubMed PMID: 27795621. PMCID: PMC5067335. Epub 20161004.","DOI":"10.1155\/2016\/3635809"},{"key":"74","doi-asserted-by":"crossref","unstructured":"Bischoff-Ferrari HA, Dawson-Hughes B, Stocklin E, Sidelnikov E, Willett WC, Edel JO, Stahelin HB, Wolfram S, Jetter A, Schwager J, Henschkowski J, von Eckardstein A, Egli A. Oral supplementation with 25(OH)D3 versus vitamin D3: Effects on 25(OH)D levels, lower extremity function, blood pressure, and markers of innate immunity. J Bone Miner Res. 2012;27(1):160\u20139. PubMed PMID: 22028071. Epub 2011\/10\/27. eng.","DOI":"10.1002\/jbmr.551"},{"key":"75","doi-asserted-by":"crossref","unstructured":"Nielsen OH, Hansen TI, Gubatan JM, Jensen KB, Rejnmark L. Managing vitamin D deficiency in inflammatory bowel disease. Frontline Gastroenterol. 2019;10(4):394\u2013400. PubMed PMID: 31656565. PMCID: PMC6788352. Epub 2019\/10\/28.","DOI":"10.1136\/flgastro-2018-101055"},{"key":"76","unstructured":"Willett WC, Stampfer MJ, Underwood BA, Sampson LA, Hennekens CH, Wallingford JC, Cooper L, Hsieh CC, Speizer FE. Vitamin A supplementation and plasma retinol levels: A randomized trial among women. J Natl Cancer Inst. 1984;73(6):1445\u20138. PubMed PMID:6595452."},{"key":"77","doi-asserted-by":"crossref","unstructured":"Wald NJ, Cuckle HS, Barlow RD, Thompson P, Nanchahal K, Blow RJ, Brown I, Harling CC, McCulloch WJ, Morgan J, Reid AR. The effect of vitamin A supplementation on serum retinol and retinol binding protein levels. Cancer Lett. 1985;29(2):203\u201313.","DOI":"10.1016\/0304-3835(85)90160-0"}],"container-title":["Critical Reviews in Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.dl.begellhouse.com\/download\/article\/7071eb52124456eb\/CRI-62974.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:32:44Z","timestamp":1790793164000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.dl.begellhouse.com\/journals\/2ff21abf44b19838,3cd8f7141fb7b275,7071eb52124456eb.html"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026]]},"references-count":77,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026]]}},"URL":"https:\/\/doi.org\/10.1615\/critrevimmunol.2026062974","relation":{},"ISSN":["1040-8401"],"issn-type":[{"value":"1040-8401","type":"print"}],"subject":[],"published":{"date-parts":[[2026]]}}}