{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T06:05:06Z","timestamp":1784613906939,"version":"3.55.0"},"reference-count":24,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82402017, 82502089"],"award-info":[{"award-number":["82402017, 82502089"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2025M772054"],"award-info":[{"award-number":["2025M772054"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"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>Necrotizing enterocolitis (NEC) is a devastating inflammatory disease of prematurity, yet how it reshapes systemic immunity relative to normal postnatal immune maturation remains unclear. We sought to define the peripheral immune architecture of NEC within a developmental framework and to evaluate whether its dominant signal could be linked to intestinal pathology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed high-dimensional Cytometry by Time-of-Flight profiling on 45 peripheral blood samples from 40 preterm infants spanning birth, postnatal control, pre-onset NEC, NEC onset, and post-onset NEC. Peripheral immune states were modeled relative to a birth-to-postnatal developmental reference trajectory. Key findings were further examined in publicly available intestinal single-cell and bulk transcriptomic datasets, and monocyte human leukocyte antigen-DR (HLA-DR) intensity was assessed as a simplified protein-level metric.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Twenty-seven immune cell subtypes were resolved across major lymphoid and myeloid compartments. In controls, peripheral immunity followed a stereotyped transition from early myeloid predominance toward lymphoid expansion after birth. NEC onset was associated with marked deviation from this trajectory and was dominated by expansion of HLA-DR-low CD16-negative monocytes, contraction of naive and regulatory T-cell subsets, and rewiring of immune correlations toward a myeloid-centered network. Cross-platform analyses supported concordance between the peripheral HLA-DR-low monocyte signal and inflammatory intestinal myeloid states with reduced antigen-presentation programs. Lower monocyte HLA-DR correlated with inflammatory severity; an exploratory within-cohort ROC analysis yielded an area under the curve of 0.84 (95% confidence interval 0.65-0.99).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>NEC is associated with developmentally discordant systemic immune remodeling centered on an HLA-DR-low monocyte state in blood, with concordant intestinal myeloid signatures in independent datasets. Monocyte HLA-DR may serve as a mechanistically anchored candidate readout for immune monitoring in preterm infants with NEC, pending external validation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1868823","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T05:35:29Z","timestamp":1784612129000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Peripheral immune profiling identifies developmental immune displacement into an HLA-DR-low monocyte state in necrotizing enterocolitis"],"prefix":"10.3389","volume":"17","author":[{"given":"Yihuang","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Neonatology, Children\u2019s Hospital of Fudan University, National Children\u2019s Medical Center","place":["Shanghai, 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