Qian et al. shows that ILC2s can be generated from not only thymic multipotent progenitors but also committed T cell precursors. These processes are greatly suppressed by E protein transcription factors. Thymic ILC2s show functional differences from those made elsewhere.

Innate lymphoid cells (ILCs) are important regulators in various immune responses. Current paradigm states that all newly-made ILCs originate from common lymphoid progenitors (CLP) in the bone marrow. Id2, an inhibitor of E protein transcription factors, is indispensable for ILC differentiation. Unexpectedly, we found that ectopically expressing Id1 or deleting two E protein genes in the thymus drastically increased ILC2 counts in the thymus and other organs where ILC2 normally reside. Further evidence suggests a thymic origin of these mutant ILC2s. The mutant mice exhibit augmented spontaneous infiltration of eosinophils and heightened responses to papain in the lung and increased ability to expulse the helminth parasite, Nippostrongylus brasiliensis. These results prompt the question whether the thymus naturally has the capacity to produce ILC2s and E proteins restrain such a potential. The abundance of ILC2s in Id1 transgenic mice also offers a unique opportunity for testing the biological functions of ILC2s.

Background:The FANCA (Fanconi anemia complementation group A) gene is mutated in ϳ60% of Fanconi anemia patients, but no biochemical activity has been identified. Results: Purified FANCA binds to nucleic acids of a certain length through its C terminus. Conclusion: FANCA has an intrinsic affinity for nucleic acids with a strong preference for single-stranded forms. Significance: Unveiling the biochemical activity of FANCA is critical for understanding its functions in DNA repair.

The Y-family of DNA polymerases support of translesion DNA synthesis (TLS) associated with stalled DNA replication by DNA damage. Recently, a number of studies suggest that some specialized TLS polymerases also support other aspects of DNA metabolism beyond TLS in vivo. Here we show that mouse polymerase kappa (Polκ) could accumulate at laser-induced sites of damage in vivo resembling polymerases eta and iota. The recruitment was mediated through Polκ C-terminus which contains the PCNA-interacting peptide, ubiquitin zinc finger motif 2 and nuclear localization signal. Interestingly, this recruitment was significantly reduced in MSH2-deficient LoVo cells and Rad18-depleted cells. We further observed that Polκ-deficient mouse embryo fibroblasts were abnormally sensitive to H2O2 treatment and displayed defects in both single-strand break repair and double-strand break repair. We speculate that Polκ may have an important role in strand break repair following oxidative stress in vivo.

Background: 3Ј repair exonuclease 1 (TREX1) is a DNase involved in autoimmune disorders and the antiviral response. Results: TREX1 also degrades single-stranded RNA or RNA in a RNA/DNA hybrid molecule. Conclusion: TREX1 is a human homolog of Escherichia coli RNase T. Significance: The novel RNase activity of TREX1 is crucial for understanding its physiological role.