Congrats to Taneli and the rest of the team on this report of a screen performed at the DRSC!
Helenius IT, Haake RJ, Kwon YJ, Hu JA, Krupinski T, Casalino-Matsuda SM, Sporn PH, Sznajder JI, Beitel GJ. Identification of Drosophila Zfh2 as a Mediator of Hypercapnic Immune Regulation by a Genome-Wide RNA Interference Screen. J Immunol. 2015 Dec 7. pii: 1501708. PMID: 26643480.
From the abstract: "Hypercapnia, elevated partial pressure of CO2 in blood and
tissue, develops in many patients with chronic severe obstructive
pulmonary disease and other advanced lung disorders. Patients with
advanced disease frequently develop bacterial lung infections ... We
previously demonstrated that hypercapnia suppresses induction of
NF-κB-regulated innate immune response genes ... However, the molecular
mediators of hypercapnic immune suppression are undefined. In this
study, we report a genome-wide RNA interference screen in Drosophila S2*
cells stimulated with bacterial peptidoglycan. The screen identified 16
genes with human orthologs whose knockdown reduced hypercapnic
suppression of the gene encoding the antimicrobial peptide Diptericin
(Dipt), but did not increase Dipt mRNA levels in air. In vivo tests of
one of the strongest screen hits, zinc finger homeodomain 2 (Zfh2;
mammalian orthologs ZFHX3/ATBF1 and ZFHX4), demonstrate that reducing
zfh2 function using a mutation or RNA interference improves survival of
flies exposed to elevated CO2 and infected with
Staphylococcus aureus. Tissue-specific knockdown of zfh2 in the fat
body, the major immune and metabolic organ of the fly, mitigates
hypercapnia-induced reductions ...
and improves resistance of CO2-exposed flies to infection.
Zfh2 mutations also partially rescue hypercapnia-induced delays in egg
hatching ... Taken together, to our
knowledge, these results identify Zfh2 as the first in vivo mediator of
hypercapnic immune suppression."
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