{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:00:51Z","timestamp":1785427251240,"version":"3.56.0"},"posted":{"date-parts":[[2025,7,6]]},"group-title":"Immunology","reference-count":50,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,7,6]],"date-time":"2025-07-06T00:00:00Z","timestamp":1751760000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,7,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background and Aims<\/jats:title>\n                  <jats:p>\n                    Immune responses to infection must balance pathogen clearance with minimizing tissue damage and autoimmunity. Chronic gastric inflammation caused by\n                    <jats:italic>H. pylori<\/jats:italic>\n                    damages the gastric mucosa and promotes carcinogenesis. Glucocorticoids are immunoregulatory hormones that limit immune activation in the stomach. This study aimed to determine how endogenous glucocorticoids regulate the gastric immune response to\n                    <jats:italic>Helicobacter<\/jats:italic>\n                    infection and their impact on preneoplastic lesion development.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    We examined the role of endogenous glucocorticoids in shaping the gastric immune response to\n                    <jats:italic>Helicobacter felis<\/jats:italic>\n                    colonization. Gastric immune cell infiltration, atrophy, metaplasia, and preneoplastic lesion development were evaluated in adrenal-intact control mice and adrenalectomized (ADX) mice. Auto-reactive IgG antibodies were assessed using a mouse self-antigen array and by measuring their binding to healthy gastric tissue.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    Loss of endogenous glucocorticoids led to significantly increased\n                    <jats:italic>H. felis-<\/jats:italic>\n                    induced gastric T cell infiltration and proinflammatory cytokine expression compared to intact-infected controls. While all intact mice maintained chronic infection for up to 12 months, nearly all ADX mice eradicated\n                    <jats:italic>H. felis<\/jats:italic>\n                    within 2\u20133 weeks. Despite bacterial clearance, ADX mice continued to exhibit chronic gastric inflammation and developed dysplasia. Autoantibody profiling showed that both intact and ADX groups generated self-reactive IgG during active infection. However, only ADX mice sustained autoantibody production following bacterial eradication.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>\n                    Endogenous glucocorticoids attenuate gastric inflammation during\n                    <jats:italic>Helicobacter<\/jats:italic>\n                    infection, supporting bacterial persistence while maintaining immune tolerance. These findings suggest that heightened immune responses to\n                    <jats:italic>H. pylori<\/jats:italic>\n                    may trigger autoimmune gastritis (AIG) development, which can persist after\n                    <jats:italic>H. pylori<\/jats:italic>\n                    clearance and continue to drive gastric cancer risk.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.07.03.662976","type":"posted-content","created":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T00:05:33Z","timestamp":1751846733000},"source":"Crossref","is-referenced-by-count":0,"title":["Endogenous glucocorticoids moderate the gastric inflammatory response to\n                  <i>Helicobacter<\/i>\n                  infection and protect from autoimmunity"],"prefix":"10.64898","author":[{"given":"Sara R.","family":"Druffner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin C.","family":"Duncan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maeve T.","family":"Morris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan L.","family":"Pascoe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyler M.","family":"Abner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salik","family":"Hussain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M Blanca","family":"Piazuelo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Richard M.","family":"Peek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melody","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J.","family":"DiPaolo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan T.","family":"Busada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025070908000767000_2025.07.03.662976v1.1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21492"},{"key":"2025070908000767000_2025.07.03.662976v1.2","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2022-327827"},{"key":"2025070908000767000_2025.07.03.662976v1.3","doi-asserted-by":"crossref","unstructured":"Chen C , Yang Y , Li P , Hu H . 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