{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T06:43:05Z","timestamp":1776235385988,"version":"3.50.1"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:00:00Z","timestamp":1776211200000},"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>Introduction<\/jats:title>\n                    <jats:p>\n                      Very early-onset inflammatory bowel disease (VEO-IBD) is frequently triggered by monogenic defects in the pathways responsible for immune system regulation, including mutations in the interleukin-10 receptor alpha (\n                      <jats:italic>IL-10RA<\/jats:italic>\n                      ) gene. Patients often show severe and refractory clinical manifestations. Thalidomide has shown immunomodulatory effects in pediatric IBD; however, its immunological effects in\n                      <jats:italic>IL-10RA<\/jats:italic>\n                      -associated VEO-IBD remain poorly defined.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A female patient aged 2 months diagnosed with VEO-IBD was enrolled in the study. Clinical data were gathered over time. Whole-exome sequencing was utilized to uncover pathogenic variants for genomic analysis. The expression of\n                      <jats:italic>IL-10RA<\/jats:italic>\n                      was assessed using Western blotting. Flow cytometry was performed both before and after treatment to evaluate the effect of the administration of thalidomide on the populations of T and B lymphocytes, alongside the immune activation levels.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The patient experienced chronic diarrhea, failure to thrive, and recurrent infections. Genetic analysis revealed the presence of compound heterozygous mutations in the\n                      <jats:italic>IL-10RA<\/jats:italic>\n                      gene (c.301C&amp;gt;T and c.537G&amp;gt;A). Western blotting analysis revealed a reduction in the levels of IL-10RA protein expression. Immunophenotyping showed an increase in the percentages of \u03b3\u03b4 T cells, Th17 cells, transitional B cells, and activated CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells before treatment. After thalidomide therapy, the symptoms of diarrhea resolved, the growth parameters improved, the proportions of \u03b3\u03b4 T cells and transitional B cells decreased, and the inflammatory markers returned to normal levels.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      This study confirms the immune dysregulation caused by\n                      <jats:italic>IL-10RA<\/jats:italic>\n                      gene mutation in VEO-IBD and demonstrates that thalidomide treatment can improve clinical symptoms and modulate specific lymphocyte subsets. The immune mechanisms behind the response to thalidomide in\n                      <jats:italic>IL-10RA<\/jats:italic>\n                      -associated VEO-IBD should be further explored.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1748151","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T05:42:20Z","timestamp":1776231740000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Thalidomide-mediated immunomodulation in a patient with IL-10RA deficiency-associated very early-onset inflammatory bowel disease"],"prefix":"10.3389","volume":"17","author":[{"given":"Aiyan","family":"Ren","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Affiliated Hospital of Zunyi Medical University","place":["Zunyi, China"]},{"name":"Guizhou Children\u2019s Hospital","place":["Zunyi, 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