{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T09:06:23Z","timestamp":1789635983473,"version":"4.0.0"},"reference-count":139,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"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:p>\n                    Diabetic kidney disease (DKD) is one of the most common microvascular complications of diabetes and a leading cause of end-stage renal disease. Recently, immune and inflammatory mechanisms have been recognized as critical in the pathogenesis of DKD, among which CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell subset imbalance serves as a key contributor to renal inflammation and fibrosis. This narrative review synthesizes evidence from PubMed, Web of Science, and EMBASE (inception to March 2026) to provide a comprehensive overview of the immunopathological roles and molecular regulatory networks of major CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell subsets, including T helper type 1, T helper type 2, T helper type 17 and regulatory T cells, in mediating renal injury through signature cytokines and signaling pathways. We also discuss the regulatory effects of hyperglycemia, hypoxia and lipid disorders on CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell function, as well as the crosstalk between renal resident cells and CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells via pathways such as programmed death-1\/programmed death ligand-1 and nuclear factor-kappa B in amplifying inflammatory responses. Moreover, we outline current therapeutic strategies targeting CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells, including traditional Chinese herbs, biologic agents, nonsteroidal mineralocorticoid receptor antagonists, sodium-glucose cotransporter 2 inhibitors and stem cell therapy, and evaluate their potential and limitations in balancing T cell subsets and alleviating renal injury. Although these approaches show promise, translating them into precise immunotherapy for DKD will require deeper mechanistic insight and rigorous clinical validation.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1882303","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T08:52:06Z","timestamp":1789635126000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["CD4+ T cell subset imbalance contributes to diabetic kidney disease progression: immunopathological mechanisms and targeted therapeutic strategies"],"prefix":"10.3389","volume":"17","author":[{"given":"Dingchang","family":"Zheng","sequence":"first","affiliation":[{"name":"CuiYing Honors College, Lanzhou University","place":["Lanzhou, Gansu, China"]},{"name":"The First Clinical Medical College, Lanzhou University","place":["Lanzhou, Gansu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingfei","family":"Zhang","sequence":"additional","affiliation":[{"name":"CuiYing Honors College, Lanzhou University","place":["Lanzhou, Gansu, China"]},{"name":"The Second Clinical Medical College, Lanzhou University","place":["Lanzhou, Gansu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hang","family":"Li","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College, Lanzhou University","place":["Lanzhou, Gansu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deping","family":"Wang","sequence":"additional","affiliation":[{"name":"The Second Clinical Medical College, Lanzhou University","place":["Lanzhou, Gansu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caihong","family":"Jiao","sequence":"additional","affiliation":[{"name":"Longnan First People\u2019s Hospital","place":["Longnan, Gansu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolong","family":"Li","sequence":"additional","affiliation":[{"name":"Zhangye Second People\u2019s Hospital","place":["Zhangye, Gansu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songbo","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, First Hospital of Lanzhou University","place":["Lanzhou, Gansu, China"]},{"name":"Gansu Provincial Clinical Research Center for Endocrine Disease","place":["Lanzhou, Gansu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms251810051","article-title":"Molecular therapeutics for diabetic kidney disease: an update","volume":"25","author":"Guo","year":"2024","journal-title":"Int J Mol 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