Bone Marrow Transplantation Rescues Monocyte Recruitment Defect and Improves Cystic Fibrosis in Mice

Zhichao Fan, Elise Pitmon, Lai Wen, Jacqueline Miller, Erik Ehinger, Rana Herro, Wei Liu, Ju Chen, Zbigniew Mikulski, Douglas J. Conrad, Alex Marki, Marco Orecchioni, Puja Kumari, Yanfang Peipei Zhu, Paola M. Marcovecchio, Catherine C. Hedrick, Craig A. Hodges, Vijay A. Rathinam, Kepeng Wang, Klaus Ley

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Cystic fibrosis (CF) is an inherited life-threatening disease accompanied by repeated lung infections and multiorgan inflammation that affects tens of thousands of people worldwide. The causative gene, cystic fibrosis transmembrane conductance regulator (CFTR), is mutated in CF patients. CFTR functions in epithelial cells have traditionally been thought to cause the disease symptoms. Recent work has shown an additional defect: monocytes from CF patients show a deficiency in integrin activation and adhesion. Because monocytes play critical roles in controlling infections, defective monocyte function may contribute to CF progression. In this study, we demonstrate that monocytes from CFTRDF508 mice (CF mice) show defective adhesion under flow. Transplanting CF mice with wild-type (WT) bone marrow after sublethal irradiation replaced most (60-80%) CF monocytes with WT monocytes, significantly improved survival, and reduced inflammation. WT/CF mixed bone marrow chimeras directly demonstrated defective CF monocyte recruitment to the bronchoalveolar lavage and the intestinal lamina propria in vivo. WT mice reconstituted with CF bone marrow also show lethality, suggesting that the CF defect in monocytes is not only necessary but also sufficient to cause disease. We also show that monocyte-specific knockout of CFTR retards weight gains and exacerbates dextran sulfate sodium-induced colitis. Our findings show that providing WT monocytes by bone marrow transfer rescues mortality in CF mice, suggesting that similar approaches may mitigate disease in CF patients.

Original languageEnglish (US)
Pages (from-to)745-752
Number of pages8
JournalJournal of Immunology
Issue number3
StatePublished - Feb 1 2022
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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