Role of CD4 T cell mannose binding lectin in <i>Schistosoma</i>-induced pulmonary hypertension

Claudia Mickael; Dara C. Fonseca Balladares; Rahul Kumar; Michael H. Lee; Kevin Nolan; Linda Sanders; Katie J. Tuscan; Ramraj Prasad; Pilar Londono; Fernanda P. Oliveira; Kennedi B. Pyper; Ari B. Molofsky; Rubin M. Tuder; Kurt R. Stenmark; Brian B. Graham

doi:10.1172/jci.insight.202919

¹Division of Pulmonary Sciences and Critical Care Medicine, Department of Me, University of Colorado Anschutz Medical Campus, Aurora, United States of America

²Department of Medicine, UCSF, San Francisco, United States of America

³Department of Translational Immunology, Genentech Inc., South San Francisco, United States of America

⁴Cardiovascular Pulmonary Research Lab, University of Colorado Anschutz Medical Campus, Aurora, United States of America

⁵Division of Respiratory Diseases, Federal University of São Paul, São Paul, Brazil

⁶Department of Laboratory Medicine, UCSF, San Francisco, United States of America

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¹Division of Pulmonary Sciences and Critical Care Medicine, Department of Me, University of Colorado Anschutz Medical Campus, Aurora, United States of America

²Department of Medicine, UCSF, San Francisco, United States of America

³Department of Translational Immunology, Genentech Inc., South San Francisco, United States of America

⁴Cardiovascular Pulmonary Research Lab, University of Colorado Anschutz Medical Campus, Aurora, United States of America

⁵Division of Respiratory Diseases, Federal University of São Paul, São Paul, Brazil

⁶Department of Laboratory Medicine, UCSF, San Francisco, United States of America

Find articles by Fonseca Balladares, D. in: PubMed | Google Scholar

¹Division of Pulmonary Sciences and Critical Care Medicine, Department of Me, University of Colorado Anschutz Medical Campus, Aurora, United States of America

²Department of Medicine, UCSF, San Francisco, United States of America

³Department of Translational Immunology, Genentech Inc., South San Francisco, United States of America

⁴Cardiovascular Pulmonary Research Lab, University of Colorado Anschutz Medical Campus, Aurora, United States of America

⁵Division of Respiratory Diseases, Federal University of São Paul, São Paul, Brazil

⁶Department of Laboratory Medicine, UCSF, San Francisco, United States of America

Find articles by Kumar, R. in: PubMed | Google Scholar |

¹Division of Pulmonary Sciences and Critical Care Medicine, Department of Me, University of Colorado Anschutz Medical Campus, Aurora, United States of America

²Department of Medicine, UCSF, San Francisco, United States of America

³Department of Translational Immunology, Genentech Inc., South San Francisco, United States of America

⁴Cardiovascular Pulmonary Research Lab, University of Colorado Anschutz Medical Campus, Aurora, United States of America

⁵Division of Respiratory Diseases, Federal University of São Paul, São Paul, Brazil

⁶Department of Laboratory Medicine, UCSF, San Francisco, United States of America

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¹Division of Pulmonary Sciences and Critical Care Medicine, Department of Me, University of Colorado Anschutz Medical Campus, Aurora, United States of America

²Department of Medicine, UCSF, San Francisco, United States of America

³Department of Translational Immunology, Genentech Inc., South San Francisco, United States of America

⁴Cardiovascular Pulmonary Research Lab, University of Colorado Anschutz Medical Campus, Aurora, United States of America

⁵Division of Respiratory Diseases, Federal University of São Paul, São Paul, Brazil

⁶Department of Laboratory Medicine, UCSF, San Francisco, United States of America

Find articles by Nolan, K. in: PubMed | Google Scholar

¹Division of Pulmonary Sciences and Critical Care Medicine, Department of Me, University of Colorado Anschutz Medical Campus, Aurora, United States of America

²Department of Medicine, UCSF, San Francisco, United States of America

³Department of Translational Immunology, Genentech Inc., South San Francisco, United States of America

⁴Cardiovascular Pulmonary Research Lab, University of Colorado Anschutz Medical Campus, Aurora, United States of America

⁵Division of Respiratory Diseases, Federal University of São Paul, São Paul, Brazil

⁶Department of Laboratory Medicine, UCSF, San Francisco, United States of America

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¹Division of Pulmonary Sciences and Critical Care Medicine, Department of Me, University of Colorado Anschutz Medical Campus, Aurora, United States of America

²Department of Medicine, UCSF, San Francisco, United States of America

³Department of Translational Immunology, Genentech Inc., South San Francisco, United States of America

⁴Cardiovascular Pulmonary Research Lab, University of Colorado Anschutz Medical Campus, Aurora, United States of America

⁵Division of Respiratory Diseases, Federal University of São Paul, São Paul, Brazil

⁶Department of Laboratory Medicine, UCSF, San Francisco, United States of America

Find articles by Tuscan, K. in: PubMed | Google Scholar

¹Division of Pulmonary Sciences and Critical Care Medicine, Department of Me, University of Colorado Anschutz Medical Campus, Aurora, United States of America

²Department of Medicine, UCSF, San Francisco, United States of America

³Department of Translational Immunology, Genentech Inc., South San Francisco, United States of America

⁴Cardiovascular Pulmonary Research Lab, University of Colorado Anschutz Medical Campus, Aurora, United States of America

⁵Division of Respiratory Diseases, Federal University of São Paul, São Paul, Brazil

⁶Department of Laboratory Medicine, UCSF, San Francisco, United States of America

Find articles by Prasad, R. in: PubMed | Google Scholar

¹Division of Pulmonary Sciences and Critical Care Medicine, Department of Me, University of Colorado Anschutz Medical Campus, Aurora, United States of America

²Department of Medicine, UCSF, San Francisco, United States of America

³Department of Translational Immunology, Genentech Inc., South San Francisco, United States of America

⁴Cardiovascular Pulmonary Research Lab, University of Colorado Anschutz Medical Campus, Aurora, United States of America

⁵Division of Respiratory Diseases, Federal University of São Paul, São Paul, Brazil

⁶Department of Laboratory Medicine, UCSF, San Francisco, United States of America

Find articles by Londono, P. in: PubMed | Google Scholar

¹Division of Pulmonary Sciences and Critical Care Medicine, Department of Me, University of Colorado Anschutz Medical Campus, Aurora, United States of America

²Department of Medicine, UCSF, San Francisco, United States of America

³Department of Translational Immunology, Genentech Inc., South San Francisco, United States of America

⁴Cardiovascular Pulmonary Research Lab, University of Colorado Anschutz Medical Campus, Aurora, United States of America

⁵Division of Respiratory Diseases, Federal University of São Paul, São Paul, Brazil

⁶Department of Laboratory Medicine, UCSF, San Francisco, United States of America

Find articles by Oliveira, F. in: PubMed | Google Scholar

¹Division of Pulmonary Sciences and Critical Care Medicine, Department of Me, University of Colorado Anschutz Medical Campus, Aurora, United States of America

²Department of Medicine, UCSF, San Francisco, United States of America

³Department of Translational Immunology, Genentech Inc., South San Francisco, United States of America

⁴Cardiovascular Pulmonary Research Lab, University of Colorado Anschutz Medical Campus, Aurora, United States of America

⁵Division of Respiratory Diseases, Federal University of São Paul, São Paul, Brazil

⁶Department of Laboratory Medicine, UCSF, San Francisco, United States of America

Find articles by Pyper, K. in: PubMed | Google Scholar

¹Division of Pulmonary Sciences and Critical Care Medicine, Department of Me, University of Colorado Anschutz Medical Campus, Aurora, United States of America

²Department of Medicine, UCSF, San Francisco, United States of America

³Department of Translational Immunology, Genentech Inc., South San Francisco, United States of America

⁴Cardiovascular Pulmonary Research Lab, University of Colorado Anschutz Medical Campus, Aurora, United States of America

⁵Division of Respiratory Diseases, Federal University of São Paul, São Paul, Brazil

⁶Department of Laboratory Medicine, UCSF, San Francisco, United States of America

Find articles by Molofsky, A. in: PubMed | Google Scholar

¹Division of Pulmonary Sciences and Critical Care Medicine, Department of Me, University of Colorado Anschutz Medical Campus, Aurora, United States of America

²Department of Medicine, UCSF, San Francisco, United States of America

³Department of Translational Immunology, Genentech Inc., South San Francisco, United States of America

⁴Cardiovascular Pulmonary Research Lab, University of Colorado Anschutz Medical Campus, Aurora, United States of America

⁵Division of Respiratory Diseases, Federal University of São Paul, São Paul, Brazil

⁶Department of Laboratory Medicine, UCSF, San Francisco, United States of America

Find articles by Tuder, R. in: PubMed | Google Scholar

¹Division of Pulmonary Sciences and Critical Care Medicine, Department of Me, University of Colorado Anschutz Medical Campus, Aurora, United States of America

²Department of Medicine, UCSF, San Francisco, United States of America

³Department of Translational Immunology, Genentech Inc., South San Francisco, United States of America

⁴Cardiovascular Pulmonary Research Lab, University of Colorado Anschutz Medical Campus, Aurora, United States of America

⁵Division of Respiratory Diseases, Federal University of São Paul, São Paul, Brazil

⁶Department of Laboratory Medicine, UCSF, San Francisco, United States of America

Find articles by Stenmark, K. in: PubMed | Google Scholar |

¹Division of Pulmonary Sciences and Critical Care Medicine, Department of Me, University of Colorado Anschutz Medical Campus, Aurora, United States of America

²Department of Medicine, UCSF, San Francisco, United States of America

³Department of Translational Immunology, Genentech Inc., South San Francisco, United States of America

⁴Cardiovascular Pulmonary Research Lab, University of Colorado Anschutz Medical Campus, Aurora, United States of America

⁵Division of Respiratory Diseases, Federal University of São Paul, São Paul, Brazil

⁶Department of Laboratory Medicine, UCSF, San Francisco, United States of America

Find articles by Graham, B. in: PubMed | Google Scholar |

JCI Insight. https://doi.org/10.1172/jci.insight.202919.
Copyright © 2026, Mickael et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

Published July 28, 2026 - Version history

Schistosomiasis is a common cause of pulmonary hypertension (PH) worldwide. It is known that adaptive immunity and specifically CD4 T cells are necessary for experimental disease pathogenesis. The lectin complement system is activated in those infected with schistosomiasis. We tested the hypothesis that lectin complement promotes Th2 CD4 T cell activation, leading to PH in a schistosomiasis exposure model. Wildtype and transgenic mice lacking mannose binding lectin (MBL), and bone marrow chimeras, were experimentally exposed to Schistosoma mansoni eggs. PH severity was assessed by hemodynamics and vascular remodeling, and CD4 T cell density and phenotype was assessed by flow cytometry. Wildtype recipients of MBL knockout bone marrow (BM) were protected from Schistosoma-induced PH. The protection from PH was associated with fewer Th2 CD4 T cells. In wildtype mice exposed to Schistosoma, CD4 T cells expression of MBL increased. MBL-deficient CD4 T cells had a suppressed Th2 phenotype when exposed to Schistosoma antigens. Mice with deficiency of C4, which functions downstream of MBL in the lectin complement pathway, were not protected from Schistosoma-PH. Mice lacking MBL were not protected from PH caused by hypoxia exposure. MBL in CD4 T cells promotes Schistosoma-induced PH.

Version 1 (July 28, 2026): In-Press Preview

Role of CD4 T cell mannose binding lectin in Schistosoma-induced pulmonary hypertension

Claudia Mickael,¹ Dara C. Fonseca Balladares,² Rahul Kumar,³ Michael H. Lee,² Kevin Nolan,² Linda Sanders,¹ Katie J. Tuscan,¹ Ramraj Prasad,⁴ Pilar Londono,¹ Fernanda P. Oliveira,⁵ Kennedi B. Pyper,⁶ Ari B. Molofsky,⁶ Rubin M. Tuder,¹ Kurt R. Stenmark,⁴ and Brian B. Graham²

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Role of CD4 T cell mannose binding lectin in Schistosoma-induced pulmonary hypertension

Claudia Mickael,1 Dara C. Fonseca Balladares,2 Rahul Kumar,3 Michael H. Lee,2 Kevin Nolan,2 Linda Sanders,1 Katie J. Tuscan,1 Ramraj Prasad,4 Pilar Londono,1 Fernanda P. Oliveira,5 Kennedi B. Pyper,6 Ari B. Molofsky,6 Rubin M. Tuder,1 Kurt R. Stenmark,4 and Brian B. Graham2

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Claudia Mickael,¹ Dara C. Fonseca Balladares,² Rahul Kumar,³ Michael H. Lee,² Kevin Nolan,² Linda Sanders,¹ Katie J. Tuscan,¹ Ramraj Prasad,⁴ Pilar Londono,¹ Fernanda P. Oliveira,⁵ Kennedi B. Pyper,⁶ Ari B. Molofsky,⁶ Rubin M. Tuder,¹ Kurt R. Stenmark,⁴ and Brian B. Graham²