The human fetal lung develops gradually, resulting in development of a functional respiratory system enabling respiration upon birth. The formation of the terminal bronchioles and alveolar duct starts at the pseudoglandular stage, which depends on finetuned signaling between lung epithelial progenitors and surrounding cells. However, the co-development of the immune compartment on tissue morphogenesis is unclear. Therefore, we collected human fetal lung tissue from the pseudoglandular stage at week 8, 10, 12 and 14 to visualize a) lung structural and b) immune cells by Imaging Mass Cytometry (IMC).

We observed glandular-like structures at all the weeks, expressing the epithelial marker E-cadherin and the proliferation marker Ki-67. These structures were surrounded by cells expressing the neuronal/NK cell marker CD56. CD45⁺ immune cells were observed in the 10, 12 and 14 week samples, and included naïve CD45RA⁺CD3⁺CD7⁺ T lymphocytes and CD45RA⁺CD3^-CD7⁺ innate lymphoid cells. CD11c⁺ myeloid cells and HLA-DR⁺ antigen presenting cells were also observed in the 12 and 14 week samples.

In summary, immune cells occur at the pseudoglandular stage and spatial visualization in the developing fetal lung indicates a dynamic organization of the structural and cellular immune compartment. Our next step is to explore the interactions of immune cells with lung epithelial cells, to clarify the interactions between the developing lung and the immune system.

Li Jia is supported by a Chinese Scholarship Council fellowship (#201906170073); P. Padmini S.J. Khedoe is supported by a grant from Air2020.