Jeng-Chang Chen , Liang-Shiou Ou , Ming-Ling Kuo , Li-Yun Tseng , Hsueh-Ling Chang
{"title":"小鼠胎儿暴露于自身抗原会诱发非致病性自身免疫","authors":"Jeng-Chang Chen , Liang-Shiou Ou , Ming-Ling Kuo , Li-Yun Tseng , Hsueh-Ling Chang","doi":"10.1016/j.arcmed.2024.103013","DOIUrl":null,"url":null,"abstract":"<div><h3>Background and aim</h3><p>Autoimmunity refers to the presence of autoantibodies and autoreactive lymphocytes against the structural molecules of an individual's cells or tissues, known as self-antigens or autoantigens. It might exist in the absence of autoimmune disease. However, how autoimmunity develops remains a mystery, despite the discovery of autoantibodies in human cord blood.</p></div><div><h3>Methods</h3><p>Murine fetuses on day 14 of gestation were subjected to intraperitoneal injection of murine thyroid peroxidase (TPO) peptides or collagen type II (CII) at graded doses via transuterine approach. Postnatally, the recipients were examined for autoantibodies by ELISA and autoreactive lymphocytes by <em>in vitro</em> incorporation of tritium and for the development of autoimmune thyroiditis or arthritis.</p></div><div><h3>Results</h3><p>At one month of age, the recipients did not secrete significant levels of anti-TPO or CII IgG<sub>2a</sub> in sera until a dose of 0.5 µg TPO or 5.0 µg CII was injected <em>in utero</em>. Serum anti-TPO or CII IgG<sub>2a</sub> persisted for at least two to four months postnatally. In recipients with elevated autoantibodies, their lymphocytes also showed proliferative responses specifically to TPO or CII. However, the development of autoantibodies and autoreactive lymphocytes was not associated with inflammatory cell infiltration of thyroid glands or paw joints even though anti-TPO or CII IgG<sub>2a</sub> was enhanced by postnatal TPO or CII challenge.</p></div><div><h3>Conclusion</h3><p>Fetal exposure to free autoantigens could be immunogenic, shedding new light on the <em>in utero</em> origin of autoantibodies and autoreactive lymphocytes. The development of autoimmunity requires a threshold intensity of autoantigen exposure in the fetus.</p></div>","PeriodicalId":8318,"journal":{"name":"Archives of Medical Research","volume":null,"pages":null},"PeriodicalIF":4.7000,"publicationDate":"2024-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Autoantigen Exposure in Murine Fetuses Elicited Nonpathogenic Autoimmunity\",\"authors\":\"Jeng-Chang Chen , Liang-Shiou Ou , Ming-Ling Kuo , Li-Yun Tseng , Hsueh-Ling Chang\",\"doi\":\"10.1016/j.arcmed.2024.103013\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background and aim</h3><p>Autoimmunity refers to the presence of autoantibodies and autoreactive lymphocytes against the structural molecules of an individual's cells or tissues, known as self-antigens or autoantigens. It might exist in the absence of autoimmune disease. However, how autoimmunity develops remains a mystery, despite the discovery of autoantibodies in human cord blood.</p></div><div><h3>Methods</h3><p>Murine fetuses on day 14 of gestation were subjected to intraperitoneal injection of murine thyroid peroxidase (TPO) peptides or collagen type II (CII) at graded doses via transuterine approach. Postnatally, the recipients were examined for autoantibodies by ELISA and autoreactive lymphocytes by <em>in vitro</em> incorporation of tritium and for the development of autoimmune thyroiditis or arthritis.</p></div><div><h3>Results</h3><p>At one month of age, the recipients did not secrete significant levels of anti-TPO or CII IgG<sub>2a</sub> in sera until a dose of 0.5 µg TPO or 5.0 µg CII was injected <em>in utero</em>. Serum anti-TPO or CII IgG<sub>2a</sub> persisted for at least two to four months postnatally. In recipients with elevated autoantibodies, their lymphocytes also showed proliferative responses specifically to TPO or CII. However, the development of autoantibodies and autoreactive lymphocytes was not associated with inflammatory cell infiltration of thyroid glands or paw joints even though anti-TPO or CII IgG<sub>2a</sub> was enhanced by postnatal TPO or CII challenge.</p></div><div><h3>Conclusion</h3><p>Fetal exposure to free autoantigens could be immunogenic, shedding new light on the <em>in utero</em> origin of autoantibodies and autoreactive lymphocytes. The development of autoimmunity requires a threshold intensity of autoantigen exposure in the fetus.</p></div>\",\"PeriodicalId\":8318,\"journal\":{\"name\":\"Archives of Medical Research\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.7000,\"publicationDate\":\"2024-06-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Archives of Medical Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0188440924000663\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Archives of Medical Research","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0188440924000663","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
Autoantigen Exposure in Murine Fetuses Elicited Nonpathogenic Autoimmunity
Background and aim
Autoimmunity refers to the presence of autoantibodies and autoreactive lymphocytes against the structural molecules of an individual's cells or tissues, known as self-antigens or autoantigens. It might exist in the absence of autoimmune disease. However, how autoimmunity develops remains a mystery, despite the discovery of autoantibodies in human cord blood.
Methods
Murine fetuses on day 14 of gestation were subjected to intraperitoneal injection of murine thyroid peroxidase (TPO) peptides or collagen type II (CII) at graded doses via transuterine approach. Postnatally, the recipients were examined for autoantibodies by ELISA and autoreactive lymphocytes by in vitro incorporation of tritium and for the development of autoimmune thyroiditis or arthritis.
Results
At one month of age, the recipients did not secrete significant levels of anti-TPO or CII IgG2a in sera until a dose of 0.5 µg TPO or 5.0 µg CII was injected in utero. Serum anti-TPO or CII IgG2a persisted for at least two to four months postnatally. In recipients with elevated autoantibodies, their lymphocytes also showed proliferative responses specifically to TPO or CII. However, the development of autoantibodies and autoreactive lymphocytes was not associated with inflammatory cell infiltration of thyroid glands or paw joints even though anti-TPO or CII IgG2a was enhanced by postnatal TPO or CII challenge.
Conclusion
Fetal exposure to free autoantigens could be immunogenic, shedding new light on the in utero origin of autoantibodies and autoreactive lymphocytes. The development of autoimmunity requires a threshold intensity of autoantigen exposure in the fetus.
期刊介绍:
Archives of Medical Research serves as a platform for publishing original peer-reviewed medical research, aiming to bridge gaps created by medical specialization. The journal covers three main categories - biomedical, clinical, and epidemiological contributions, along with review articles and preliminary communications. With an international scope, it presents the study of diseases from diverse perspectives, offering the medical community original investigations ranging from molecular biology to clinical epidemiology in a single publication.