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Expression of Piwi protein MIWI2 defines a distinct population of multiciliated cells
Gregory A. Wasserman, … , Dónal O’Carroll, Matthew R. Jones
Gregory A. Wasserman, … , Dónal O’Carroll, Matthew R. Jones
Published September 18, 2017
Citation Information: J Clin Invest. 2017;127(10):3866-3876. https://doi.org/10.1172/JCI94639.
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Concise Communication Cell biology Pulmonology

Expression of Piwi protein MIWI2 defines a distinct population of multiciliated cells

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Abstract

P-element–induced wimpy testes (Piwi) proteins are known for suppressing retrotransposon activation in the mammalian germline. However, whether Piwi protein or Piwi-dependent functions occur in the mammalian soma is unclear. Contrary to germline-restricted expression, we observed that Piwi-like Miwi2 mRNA is indeed expressed in epithelial cells of the lung in adult mice and that it is induced during pneumonia. Further investigation revealed that MIWI2 protein localized to the cytoplasm of a discrete population of multiciliated airway epithelial cells. Isolation and next-generation sequencing of MIWI2-positive multiciliated cells revealed that they are phenotypically distinct from neighboring MIWI2-negative multiciliated cells. Mice lacking MIWI2 exhibited an altered balance of airway epithelial cells, demonstrating fewer multiciliated cells and an increase in club cells. During pneumococcal pneumonia, Miwi2-deficient mice exhibited increased expression of inflammatory mediators and increased immune cell recruitment, leading to enhanced bacterial clearance. Taken together, our data delineate MIWI2-dependent functions outside of the germline and demonstrate the presence of distinct subsets of airway multiciliated cells that can be discriminated by MIWI2 expression. By demonstrating roles for MIWI2 in airway cell identity and pulmonary innate immunity, these studies elucidate unanticipated physiological functions for Piwi proteins in somatic tissues.

Authors

Gregory A. Wasserman, Aleksander D. Szymaniak, Anne C. Hinds, Kazuko Yamamoto, Hirofumi Kamata, Nicole M.S. Smith, Kristie L. Hilliard, Claudia Carrieri, Adam T. Labadorf, Lee J. Quinton, Xingbin Ai, Xaralabos Varelas, Felicia Chen, Joseph P. Mizgerd, Alan Fine, Dónal O’Carroll, Matthew R. Jones

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Figure 6

MIWI2 regulates pulmonary innate immunity during pneumonia.

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MIWI2 regulates pulmonary innate immunity during pneumonia.
(A and B) BA...
(A and B) BALF cell cytospins (A) and total BALF cell counts (B) of uninfected Miwi2+/+ and Miwi2–/– mice. n = 4, 4 mice per group, data are expressed as mean ± SEM. Microscopic images were obtained using the ×40 objective. (C–G) Total BALF cell counts (C), BALF cytospins (D), BALF differential counts (E), BALF CXCL2 protein (F), and BALF CXCL1 protein (G) were measured from Miwi2+/+ and Miwi2–/– mice infected i.t. with S. pneumoniae for 4 hours. n = 6, 7 mice per group, data are expressed as mean ± SEM. *P < 0.05, **P < 0.01 as determined by unpaired t test. Microscopic images were obtained using the ×40 objective. (H) Lung CFU was determined in Miwi2+/+ and Miwi2–/– mice infected i.t. with S. pneumoniae and harvested 30 hours later. n = 6, 9 mice per group, data represented as mean ± SEM. *P < 0.05 as determined by unpaired t test. Dotted line indicates input CFU.
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