PT  - JOURNAL ARTICLE
AU  - Gschwend, Julia
AU  - Sherman, Samantha
AU  - Ridder, Frederike
AU  - Feng, Xiaogang
AU  - Liang, Hong-Erh
AU  - Locksley, Richard M.
AU  - Becher, Burkhard
AU  - Schneider, Christoph
TI  - Alveolar macrophages strictly rely on GM-CSF from alveolar epithelial type 2 cells before and after birth
AID  - 10.1101/2021.04.01.438051
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.04.01.438051
4099  - http://biorxiv.org/content/early/2021/04/03/2021.04.01.438051.short
4100  - http://biorxiv.org/content/early/2021/04/03/2021.04.01.438051.full
AB  - Programs defining tissue-resident macrophage identity depend on local environmental cues. For alveolar macrophages (AMs), these signals are provided by immune and non-immune cells, and include GM-CSF (CSF2). However, evidence to functionally link components of this intercellular crosstalk remains scarce. We thus developed new transgenic mice to profile pulmonary GM-CSF expression, which we detected in both immune cells, including group 2 innate lymphoid cells and γδ T cells, as well as AT2s. AMs were unaffected by constitutive deletion of hematopoietic Csf2 and basophil depletion. Instead, AT2 lineage-specific constitutive and inducible Csf2 deletion revealed the non-redundant function of AT2-derived GM-CSF in instructing AM fate, establishing the postnatal AM compartment, and maintaining AMs in adult lungs. This AT2-AM relationship begins during embryogenesis, where nascent AT2s timely induce GM-CSF expression to support the proliferation and differentiation of fetal monocytes contemporaneously seeding the tissue, and persists into adulthood, when epithelial GM-CSF remains restricted to AT2s.Competing Interest StatementThe authors have declared no competing interest.