{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T15:10:41Z","timestamp":1788793841996,"version":"build-2803163510"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"content-version":"vor","delay-in-days":9,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Institut universitaire de cardiologie et de pneumologie de Qu\u00e9bec\u2013Universit\u00e9 Laval"},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Our group discovered a mutation in a French-Canadian family causing a severe and early-onset form of emphysema. The heterozygote mutation located in the PTPN6 gene causes an alanine to threonine switch near the catalytic site of SHP-1, leading to a reduction of its enzymatic activity. In this study, we aimed to characterize the respiratory and immune abnormalities caused by this mutation in human carriers (PTPN6Ala455Thr) and mice carrying the equivalent mutation (Ptpn6Ala457Thr\/+). Ptpn6Ala457Thr\/+ mice spontaneously developed pulmonary tertiary lymphoid tissues (TLTs). They also exhibited a higher proportion of B-1 cells in both lung and spleen. Ptpn6Ala457Thr\/+ mice had lower IgG1-specific antibodies to T-independent immunization, while their T-dependent response was normal. Human carriers showed reduced circulating naive B lymphocytes and increased memory B lymphocytes, a phenotype mainly observed in men, and had lower circulating levels of IgG1 and IgG4 as well as higher levels of IgG3. Spontaneous TLT formation in mice and alterations of B-cell biology in both humans and mice are caused by the mutation. This reinforces the link between emphysema, pulmonary TLT formation, and B cells; however, the exact mechanism involving B cells and pulmonary TLT in the development of emphysema remains elusive.<\/jats:p>","DOI":"10.1093\/jimmun\/vkag162","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T04:01:45Z","timestamp":1783656105000},"source":"Crossref","is-referenced-by-count":1,"title":["A mutation in\n                    <i>PTPN6<\/i>\n                    associated to emphysema alters B-lymphocyte biology in humans and mice"],"prefix":"10.1093","volume":"215","author":[{"given":"Marie","family":"Pineault","sequence":"first","affiliation":[{"name":"Institut universitaire de cardiologie et de pneumologie de Qu\u00e9bec\u2014Universit\u00e9 Laval , Quebec,","place":["Canada"]},{"name":"Faculty of Medicine, Universit\u00e9 Laval , Quebec,","place":["Canada"]},{"name":"Groupe de recherche en sant\u00e9 respiratoire de l\u2019Universit\u00e9 Laval (GESER) , 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