Camarie C. Spear’s research while affiliated with University of North Carolina at Chapel Hill and other places

Tissue-resident γδ T cells constitute a prominent source of IL-17 and IFN-γ in mucosal tissues where they provide an important first line of defense against pathogens. Unlike conventional αβ T cells, most γδ T cells are programmed during thymic development to produce either IFN-γ or IL-17. The mechanisms, however, that direct γδ T cell functional programming in the thymus remain unclear. Slam receptors are a family of nine (SLAMf1 to SLAMf9) cell surface receptors that are expressed only on hematopoietic cells and which play a central role in the host immune response. Most Slam receptors transduce signals via the small adapter protein SAP, and mice deficient in SAP exhibit numerous immunological defects. Relatively little is known, however, of the function of this signaling pathway in γδ T cells. Here, we report that distinct Slam receptor expression profiles mark functional γδ T cell subsets. Whereas SLAMf1 expression was associated with IL-17-producing CD27− RORγt+ γδ T cells, SLAMf6 expression was associated with IFNγ-producing CD27+ cells. We found that Slam receptor expression profiles were established on discrete thymic γδ T cell subsets as early as embryonic day 17 (E.17), as was the association of SLAMf1 with RORγt expression. Disruption of Slam receptor signaling by deletion of SAP resulted in a significant loss of E.17 thymic CD44hiRORγt+ γδ T cells, and a significant shift in the ratio of IFN-γ/IL-17-producing γδ T cells in both thymus and peripheral tissues. These results demonstrate for the first time that the Slam/SAP signaling pathway plays a significant role in the functional programming that regulates the γδ T cell IFN-γ/IL-17 axis during thymic development.

SCHLAP1 is a long noncoding RNA that is reported to function by depleting the SWI/SNF complex from the genome. We investigated the hypothesis that SCHLAP1 affects only specific compositions of SWI/SNF. Using several assays, we found that SWI/SNF is not depleted from the genome by SCHLAP1 and that SWI/SNF is associated with many coding and noncoding RNAs, suggesting that SCHLAP1 may function in a SWI/SNF-independent manner. © 2018, The Author(s), under exclusive licence to Springer Nature America, Inc.

SCHLAP1 is a long-noncoding RNA that is prognostic for progression to metastatic prostate cancer and promotes an invasive phenotype. SCHLAP1 is reported to function by depleting the core SWI/SNF subunit, SMARCB1, from the genome. SWI/SNF is a large, multi-subunit, chromatin remodeling complex that can be combinatorially assembled to yield hundreds to thousands of distinct complexes. Here, we investigated the hypothesis that SCHLAP1 affects only specific forms of SWI/SNF and that the remaining SWI/SNF complexes were important for the increased invasion in SCHLAP1 expressing prostate cells. Using several assays we found that SWI/SNF is not depleted from the genome by SCHLAP1 expression. We find that SCHLAP1 induces changes to chromatin openness but is not sufficient to drive changes in histone modifications. Additionally, we show that SWI/SNF binds many coding and non-coding RNAs. Together these results suggest that SCHLAP1 has roles independent of canonical SWI/SNF and that SWI/SNF broadly interacts with RNA.