Reprogramming alveolar macrophage responses to TGF-β reveals CCR2+ monocyte activity that promotes bronchiolitis obliterans syndrome

Summary

In a mouse lung transplant model, the abstract reports that extracorporeal photopheresis (ECP) lowered airway TGF-beta availability and inhibited BOS. ECP-treated leukocytes were taken up by alveolar macrophages, which became less responsive to TGF-beta and secreted decorin, an antagonist of TGF-beta. In untreated recipients, high airway TGF-beta activity led macrophages to express CCL2, which drew in CCR2-positive monocytes. Differentiation of these monocytes into monocyte-derived alveolar macrophages was required for BOS, and these macrophages expanded tissue-resident memory CD8 T cells that injured the airway through granzyme B. The findings come from mice and are not shown here to apply to people.

Details

doi

10.1172/jci159229

pmid

36189800

authors

Liu Z, Liao F, Zhu J, Zhou D, Heo GS, Leuhmann HP, Scozzi D, Parks A, Hachem R, Byers DE, Tague LK, Kulkarni HS, Cano M, Wong BW, Li W, Haung HJ, Krupnick AS, Kreisel D, Liu Y, Gelman AE

journal

Journal of Clinical Investigation

year

2022

volume

132

issue

19

articleNumber

e159229

Sources and links

• Publisher record via DOI (primary)
• PubMed 36189800

Related

Links from this record

• supports: Innate immune activation
• supports: Cytotoxic and senescent T cells
• discusses: Bronchiolitis obliterans syndrome (BOS)

Linked from (derived)

• author affiliation matches this institution (PubMed): Lung Transplant Program, University of Maryland Medical Center
• author affiliation matches this institution (PubMed): Lung Transplant Program, Washington University in St. Louis and Barnes-Jewish Hospital

Known gaps in this record

• full text not read (abstract only)
• funding statement and grant numbers
• author affiliations
• centre or centres not stated in the abstract