{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T09:14:45Z","timestamp":1790500485337,"version":"4.1.0"},"reference-count":43,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2021,8,13]],"date-time":"2021-08-13T00:00:00Z","timestamp":1628812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008431","name":"Consejer\u00eda de Educaci\u00f3n, Junta de Castilla y Le\u00f3n","doi-asserted-by":"publisher","award":["SA077P20"],"award-info":[{"award-number":["SA077P20"]}],"id":[{"id":"10.13039\/501100008431","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Haematopoiesis is a paradigm of cell differentiation because of the wide variety and overwhelming number of mature blood cells produced daily. Under stress conditions, the organism must adapt to a boosted demand for blood cells. Chronic granulomatous disease (CGD) is a genetic disease caused by inactivating mutations that affect the phagocyte oxidase. Besides a defective innate immune system, CGD patients suffer from recurrent hyper-inflammation episodes, circumstances upon which they must face emergency haematopoiesis. The targeting of Cybb and Ncf1 genes have produced CGD animal models that are a useful surrogate when studying the pathophysiology and treatment of this disease. Here, we show that Cyba\u2212\/\u2212 mice spontaneously develop granuloma and, therefore, constitute a CGD animal model to complement the existing Cybb\u2212\/\u2212 and Ncf1\u2212\/\u2212 models. More importantly, we have analysed haematopoiesis in granuloma-bearing Cyba\u2212\/\u2212 mice. These animals showed a significant loss of weight, developed remarkable splenomegaly, bone marrow myeloid hyperplasia, and signs of anaemia. Haematological analyses showed a sharped decrease of B-cells and a striking development of myeloid cells in all compartments. Collectively, our results show that granuloma inflammatory lesions dramatically change haematopoiesis homeostasis. Consequently, we suggest that besides their defective innate immunity, the alteration of haematopoiesis homeostasis upon granuloma may contribute to the dismal outcome of CGD.<\/jats:p>","DOI":"10.3390\/ijms22168701","type":"journal-article","created":{"date-parts":[[2021,8,13]],"date-time":"2021-08-13T09:22:38Z","timestamp":1628846558000},"page":"8701","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Granuloma Formation in a Cyba-Deficient Model of Chronic Granulomatous Disease Is Associated with Myeloid Hyperplasia and the Exhaustion of B-Cell Lineage"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2445-7262","authenticated-orcid":false,"given":"Rodrigo","family":"Prieto-Bermejo","sequence":"first","affiliation":[{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular, Universidad de Salamanca, 37007 Salamanca, Spain"},{"name":"IBSAL (Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca), 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2884-3398","authenticated-orcid":false,"given":"Marta","family":"Romo-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular, Universidad de Salamanca, 37007 Salamanca, Spain"},{"name":"IBSAL (Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca), 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7862-7952","authenticated-orcid":false,"given":"Alejandro","family":"P\u00e9rez-Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular, Universidad de Salamanca, 37007 Salamanca, Spain"},{"name":"IBSAL (Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca), 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5929-4926","authenticated-orcid":false,"given":"Mar\u00eda Carmen","family":"Garc\u00eda-Mac\u00edas","sequence":"additional","affiliation":[{"name":"Unidad de Patolog\u00eda Molecular Comparada, Centro de Investigaci\u00f3n del C\u00e1ncer-IBMCC (USAL-CSIC), 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"S\u00e1nchez-Bernal","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular, Universidad de Salamanca, 37007 Salamanca, Spain"},{"name":"IBSAL (Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca), 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4758-2151","authenticated-orcid":false,"given":"Ignacio","family":"Garc\u00eda-Tu\u00f1\u00f3n","sequence":"additional","affiliation":[{"name":"Unidad de Diagn\u00f3stico Molecular y Celular del C\u00e1ncer, Centro de Investigaci\u00f3n del C\u00e1ncer-IBMCC (USAL-CSIC), 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0409-3198","authenticated-orcid":false,"given":"Jes\u00fas","family":"S\u00e1nchez-Yag\u00fce","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular, Universidad de Salamanca, 37007 Salamanca, Spain"},{"name":"IBSAL (Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca), 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8370-1336","authenticated-orcid":false,"given":"Manuel","family":"S\u00e1nchez-Mart\u00edn","sequence":"additional","affiliation":[{"name":"IBSAL (Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca), 37007 Salamanca, Spain"},{"name":"Servicio de Transg\u00e9nesis, Nucleus, Universidad de Salamanca, 37007 Salamanca, Spain"},{"name":"Departamento de Medicina, Universidad de Salamanca, 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0827-7963","authenticated-orcid":false,"given":"\u00c1ngel","family":"Hern\u00e1ndez-Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular, Universidad de Salamanca, 37007 Salamanca, Spain"},{"name":"IBSAL (Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca), 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2543","DOI":"10.1007\/s12325-017-0636-2","article-title":"A Review of Chronic Granulomatous Disease","volume":"34","author":"Arnold","year":"2017","journal-title":"Adv. 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