{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T07:09:20Z","timestamp":1772521760319,"version":"3.50.1"},"reference-count":105,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T00:00:00Z","timestamp":1772496000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      A deficiency of immunosuppressive regulatory T cells, as seen in scurfy (SF) mice or in IPEX syndrome in humans, can lead to multiorgan inflammation. Oral administration of the probiotic\n                      <jats:italic>Limosilactobacillus reuteri<\/jats:italic>\n                      Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH (DSM) 17938 prolongs survival and reduces Th1- and Th2-associated inflammation in SF mice. It remains unclear how DSM 17938-educated SF-CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells modulate T-cell\u2013liver communication.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      To characterize CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells from SF mice orally administered DSM 17938 (Prob-SF-CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells) and to compare them with CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells from SF mice (SF-CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells), cells isolated from SF spleens were adoptively transferred by intraperitoneal (IP) injection into lymphocyte-deficient Recombination-Activating Gene (RAG)-1-deficient (RAG1KO) mice. Liver histological inflammation and macrophages (M\u03a6s), liver sample transcriptomes by RNAseq, and stool microbiota by 16S rRNA sequencing were then assessed in RAG1KO mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Prob-SF-CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells reduced the incidence and severity of liver inflammation and F4\/80\n                      <jats:sup>+<\/jats:sup>\n                      M\u03a6 infiltration by SF-CD4\n                      <jats:sup>+<\/jats:sup>\n                      T-cell transfer. SF-CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells upregulated genes and altered RNA splicing factors and events involved in inflammatory pathways, including Toll-like receptor (TLR) cascades, inflammatory cytokines, and death receptor signals. SF-CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells downregulated genes linked to metabolism, including mitochondrial function, the TCA cycle, lipids, and liver detoxification. Prob-CD4\n                      <jats:sup>+<\/jats:sup>\n                      T-cell transfer reversed SF-CD4\n                      <jats:sup>+<\/jats:sup>\n                      T-cell-induced gene changes in inflammatory and metabolic interactive clusters while modulating distinct genes involved in TLR regulation and the cell cycle. CD4\n                      <jats:sup>+<\/jats:sup>\n                      T-cell transfer altered gut microbial diversity compared with RAG1KO mice without CD4\n                      <jats:sup>+<\/jats:sup>\n                      T-cell transfer. Prob-SF-CD4\n                      <jats:sup>+<\/jats:sup>\n                      T-cell transfer exclusively increased the relative abundance (RA) of\n                      <jats:italic>Incertae_sedis<\/jats:italic>\n                      and reduced the RA of\n                      <jats:italic>Clostridia_vadinBB60_group<\/jats:italic>\n                      in the stool of RAG1KO mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Inflammatory lymphocytes (CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells) can perpetuate an exaggerated immune response in an immunologically na\u00efve host. Feeding with DSM 17938 modulated T cells and allowed them to provide beneficial effects to the recipient. We observed activation of multiple genes and their interactions. These findings suggest that probiotics or probiotic-modulated T cells could be further explored as therapeutic options for autoimmune liver diseases.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1713120","type":"journal-article","created":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T06:47:51Z","timestamp":1772520471000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Limosilactobacillus reuteri alleviates proinflammatory T-cell-mediated liver injury and transcriptomic changes in immunocompromised mice"],"prefix":"10.3389","volume":"17","author":[{"given":"Ana","family":"Fadhel Alvarez","sequence":"first","affiliation":[{"name":"Division of Gastroenterology, Department of Pediatrics, McGovern Medical School at UTHealth Houston","place":["Houston, TX, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zheng","family":"Yin","sequence":"additional","affiliation":[{"name":"Systems Medicine and Bioengineering Department, Houston Methodist Neal Cancer Center","place":["Houston, TX, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beanna","family":"Okeugo","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Pediatrics, McGovern Medical School at UTHealth Houston","place":["Houston, TX, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Banerjee","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, McGovern Medical School at UTHealth Houston","place":["Houston, TX, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meng","family":"Luo","sequence":"additional","affiliation":[{"name":"Microbial Genomics Resource Group, Department of Microbiology, Immunology and Parasitology, Louisiana State University Health Sciences Center","place":["New Orleans, LA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher M.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Microbial Genomics Resource Group, Department of Microbiology, Immunology and Parasitology, Louisiana State University Health Sciences Center","place":["New Orleans, LA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salomea","family":"Giorgberidze","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Pediatrics, McGovern Medical School at UTHealth Houston","place":["Houston, TX, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vaishali","family":"Harne","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Pediatrics, McGovern Medical School at UTHealth Houston","place":["Houston, TX, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rambabu","family":"Majji","sequence":"additional","affiliation":[{"name":"Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital","place":["Houston, TX, United States"]},{"name":"Department of Pediatrics, USDA\/ARS Children's Nutrition Research Center, Baylor College of Medicine","place":["Houston, TX, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melissa N.","family":"Munroe","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Pediatrics, McGovern Medical School at UTHealth Houston","place":["Houston, TX, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji Ho","family":"Suh","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Critical Care and Pain Medicine, McGovern Medical School at UTHealth Houston","place":["Houston, TX, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen T. 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