{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T17:00:04Z","timestamp":1781110804283,"version":"3.54.1"},"reference-count":49,"publisher":"National Academy of Sciences","issue":"10","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1997,5,13]]},"abstract":"<jats:p>\n                    We demonstrate that the receptor binding moiety of\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    heat-labile enterotoxin (EtxB) can completely prevent autoimmune disease in a murine model of arthritis. Injection of male DBA\/1 mice at the base of the tail with type II collagen in the presence of complete Freund\u2019s adjuvant normally leads to arthritis, as evidenced by inflammatory infiltration and swelling of the joints. A separate injection of EtxB at the same time as collagen challenge prevented leukocyte infiltration, synovial hyperplasia, and degeneration of the articular cartilage and reduced clinical symptoms of disease by 82%. The principle biological property of EtxB is its ability to bind to the ubiquitous cell surface receptor GM1 ganglioside, and to other galactose-containing glycolipids and galactoproteins. The importance of receptor interaction in mediating protection from arthritis was demonstrated by the failure of a non-receptor-binding mutant of EtxB to elicit any protective effect. Analysis of T cell responses to collagen, in cultures of draining lymph node cells, revealed that protection was associated with a marked increase in interleukin 4 production concomitant with a reduction in interferon \u03b3 levels. Furthermore, in protected mice there was a significant reduction in anti-collagen antibody levels as well as an increase in the IgG1\/IgG2a ratio. These observations show that protection is associated with a shift in the Th1\/Th2 balance as well as a general reduction in the extent of the anti-type II collagen immune response. This suggests that EtxB-receptor-mediated modulation of lymphocyte responses provides a means of preventing autoimmune disease.\n                  <\/jats:p>","DOI":"10.1073\/pnas.94.10.5290","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:40:52Z","timestamp":1027680052000},"page":"5290-5295","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":46,"title":["Prevention of autoimmune disease due to lymphocyte modulation by the B-subunit of\n                    <i>Escherichia coli<\/i>\n                    \u2009heat-labile\u2009enterotoxin"],"prefix":"10.1073","volume":"94","author":[{"given":"Neil A.","family":"Williams","sequence":"first","affiliation":[{"name":"Department of Pathology and Microbiology, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa M.","family":"Stasiuk","sequence":"additional","affiliation":[{"name":"Department of Pathology and Microbiology, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toufic O.","family":"Nashar","sequence":"additional","affiliation":[{"name":"Department of Pathology and Microbiology, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire M.","family":"Richards","sequence":"additional","affiliation":[{"name":"Department of Pathology and Microbiology, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison K.","family":"Lang","sequence":"additional","affiliation":[{"name":"Department of Pathology and Microbiology, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Day","sequence":"additional","affiliation":[{"name":"Department of Pathology and Microbiology, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy R.","family":"Hirst","sequence":"additional","affiliation":[{"name":"Department of Pathology and Microbiology, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1997,5,13]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.1.226"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/8.5.731"},{"key":"e_1_3_3_3_2","unstructured":"Nashar T.\u2009O. Hirst T.\u2009R. & Williams N.\u2009A. (1997) Immunology in press."},{"key":"e_1_3_3_4_2","first-page":"185","volume-title":"Structure and Function of Escherichia coli Heat-Labile Enterotoxin and Cholera Toxin B-Pentamer","author":"Hol W","year":"1995","unstructured":"W Hol, T K Sixma, E A Merritt Structure and Function of Escherichia coli Heat-Labile Enterotoxin and Cholera Toxin B-Pentamer, eds J Moss, B Iglewski, M Vaughan, T Tu (Dekker, New York) 9, 185\u2013224 (1995)."},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.56.7.1748-1753.1988"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.38.2.424-433.1982"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00209a021"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/283666a0"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.146.3.857"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.168.2.777"},{"key":"e_1_3_3_11_2","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.4049\/jimmunol.140.5.1477","volume":"140","author":"Seki N","year":"1988","unstructured":"N Seki, Y Sudo, T Yoshioka, S Sugihara, T Fujitsu, S Sakuma, T Ogawa, T Hamaoka, H Senoh, H Fujiwara J Immunol 140, 1477\u20131484 (1988).","journal-title":"J Immunol"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830250321"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3083.1985.tb01884.x"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.1994.tb06070.x"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.162.3.1105"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830211202"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.154.3.688"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.11.4823"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830250508"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830261020"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780390318"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830260716"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.3107127"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1006\/prep.1994.1031"},{"key":"e_1_3_3_25_2","first-page":"152","volume":"79","author":"Thompson S J","year":"1993","unstructured":"S J Thompson, H S G Thompson, N Harper, M J Day, A J Coad, C J Elson, N A Staines Immunology 79, 152\u2013157 (1993).","journal-title":"Immunology"},{"key":"e_1_3_3_26_2","first-page":"34","volume":"72","author":"Williams N A","year":"1991","unstructured":"N A Williams, T J Hill, D C Hooper Immunology 72, 34\u201339 (1991).","journal-title":"Immunology"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2567.1996.d01-760.x"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(92)90329-R"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-8411(05)80032-0"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.162.6.1878"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1006\/cimm.1996.0277"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117993"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.171.1.115"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.61.8.3459-3465.1993"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5699(95)80004-2"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.177.1.57"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.180.5.1961"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.83.19.7443"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.3109\/08916939308993327"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/5.9.1159"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.14.7196"},{"key":"e_1_3_3_42_2","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.4049\/jimmunol.154.3.1032","volume":"154","author":"Elson C O","year":"1995","unstructured":"C O Elson, S P Holland, M T Dertzbaugh, C F Cuff, A O Anderson J Immunol 154, 1032\u20131040 (1995).","journal-title":"J Immunol"},{"key":"e_1_3_3_43_2","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.4049\/jimmunol.148.7.1999","volume":"148","author":"Francis M L","year":"1992","unstructured":"M L Francis, J Ryan, M G Jobling, R K Holmes, J Moss, J J Mond J Immunol 148, 1999\u20132005 (1992).","journal-title":"J Immunol"},{"key":"e_1_3_3_44_2","doi-asserted-by":"crossref","first-page":"1750","DOI":"10.4049\/jimmunol.146.6.1750","volume":"146","author":"Gajewski T F","year":"1991","unstructured":"T F Gajewski, M Pinnas, T Wong, F W Fitch J Immunol 146, 1750\u20131758 (1991).","journal-title":"J Immunol"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.175.3.655"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.1992.tb01413.x"},{"key":"e_1_3_3_47_2","doi-asserted-by":"crossref","first-page":"519","DOI":"10.4049\/jimmunol.145.2.519","volume":"145","author":"Chiocchia G","year":"1990","unstructured":"G Chiocchia, M C Boissier, M C Ronziere, D Herbage, C Fournier J Immunol 145, 519\u2013525 (1990).","journal-title":"J Immunol"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5699(96)80556-1"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830231208"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.94.10.5290","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,22]],"date-time":"2023-04-22T08:25:14Z","timestamp":1682151914000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.94.10.5290"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1997,5,13]]},"references-count":49,"journal-issue":{"issue":"10","published-print":{"date-parts":[[1997,5,13]]}},"alternative-id":["10.1073\/pnas.94.10.5290"],"URL":"https:\/\/doi.org\/10.1073\/pnas.94.10.5290","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1997,5,13]]},"assertion":[{"value":"1996-12-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"1997-03-03","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"1997-05-13","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}