{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T16:02:10Z","timestamp":1791302530180,"version":"4.1.0"},"reference-count":44,"publisher":"National Academy of Sciences","issue":"11","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2009,3,17]]},"abstract":"<jats:p>\n                    In rheumatoid arthritis (RA), chronically stimulated T lymphocytes sustain tissue-destructive joint inflammation. Both na\u00efve and memory T cells in RA are prematurely aged with accelerated loss of telomeres suggesting excessive proliferative pressure or inadequate telomeric maintenance. Upon stimulation, RA na\u00efve CD4 T cells are defective in up-regulating telomerase activity (\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.0001) due to insufficient induction of the telomerase component human telomerase reverse transcriptase (hTERT); T cell activation and cell cycle progression are intact. Telomerase insufficiency does not affect memory T cells or CD34 hematopoietic stem cells and is present in untreated patients and independent from disease activity. Knockdown of hTERT in primary human T cells increases apoptotic propensity (\n                    <jats:italic>P<\/jats:italic>\n                    = 0.00005) and limits clonal burst (\n                    <jats:italic>P<\/jats:italic>\n                    = 0.0001) revealing a direct involvement of telomerase in T cell fate decisions. Na\u00efve RA CD4 T cells stimulated through the T cell receptor are highly susceptible to apoptosis, expanding to smaller clonal size. Overexpression of ectopic hTERT in na\u00efve RA T cells conveys apoptotic resistance (\n                    <jats:italic>P<\/jats:italic>\n                    = 0.008) and restores proliferative expansion (\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.0001). Telomerase insufficiency in RA results in excessive T cell loss, undermining homeostatic control of the naive T cell compartment and setting the stage for lymphopenia-induced T cell repertoire remodeling. Restoring defective telomerase activity emerges as a therapeutic target in resetting immune abnormalities in RA.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0811332106","type":"journal-article","created":{"date-parts":[[2009,3,2]],"date-time":"2009-03-02T21:43:19Z","timestamp":1236030199000},"page":"4360-4365","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":151,"title":["Telomerase insufficiency in rheumatoid arthritis"],"prefix":"10.1073","volume":"106","author":[{"given":"Hiroshi","family":"Fujii","sequence":"first","affiliation":[{"name":"Department of Medicine, Lowance Center for Human Immunology and Rheumatology, Emory University School of Medicine, 101 Woodruff Circle, Atlanta, GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Medicine, Lowance Center for Human Immunology and Rheumatology, Emory University School of Medicine, 101 Woodruff Circle, Atlanta, GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In\u00e9s","family":"Colmegna","sequence":"additional","affiliation":[{"name":"Department of Medicine, Lowance Center for Human Immunology and Rheumatology, Emory University School of Medicine, 101 Woodruff Circle, Atlanta, GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg J.","family":"Goronzy","sequence":"additional","affiliation":[{"name":"Department of Medicine, Lowance Center for Human Immunology and Rheumatology, Emory University School of Medicine, 101 Woodruff Circle, Atlanta, GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelia M.","family":"Weyand","sequence":"additional","affiliation":[{"name":"Department of Medicine, Lowance Center for Human Immunology and Rheumatology, Emory University School of Medicine, 101 Woodruff Circle, Atlanta, GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2009,3,17]]},"reference":[{"key":"e_1_3_3_1_2","first-page":"195","article-title":"T cell activation as starter and motor of rheumatic inflammation","volume":"305","author":"Skapenko A","year":"2006","unstructured":"A Skapenko, PE Lipsky, H Schulze-Koops, T cell activation as starter and motor of rheumatic inflammation. 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