Mapping Lung Hematopoietic Progenitors: Developmental Kinetics and Response to Influenza A Infection.

Abstract

The bone marrow is a specialized niche responsible for the maintenance of hematopoietic stem and progenitor cells during homeostasis and inflammation. Recent studies, however, have extended this essential role to the extramedullary and extravascular lung microenvironment. Here, we provide further evidence for a reservoir of hematopoietic stem and progenitor cells within the lung from Embryonic Day 18.5 until adulthood. These lung progenitors display distinct microenvironment-specific developmental kinetics compared with their bone marrow counterparts, exemplified by a rapid shift from a common myeloid to a megakaryocyte-erythrocyte progenitor-dominated niche with increasing age. In adult mice, influenza A viral infection results in a transient reduction in multipotent progenitors within the lungs, with a parallel increase in downstream granulocyte-monocyte progenitors and dendritic cell populations associated with acute viral infections. Our findings suggest that lung hematopoietic progenitors play a role in reestablishing immunological homeostasis in the respiratory mucosa, which may have significant clinical implications for maintaining pulmonary health after inflammatory perturbation.