Inflammation on the move

Effective immune responses to pathogens require the activation and differentiation of both innate and adaptive lymphocytes, such as innate lymphoid cells (ILCs) and T cells, respectively. ILCs consist of distinct helper-like subsets representing innate versions of CD4 + T helper subsets, whereas natural killer cells represent the innate counterpart of CD8 + cytotoxic T cells. By producing effector cytokines, T helper subsets and helper-like ILCs are also involved in the pathogenesis of many in-flammatory diseases. Strikingly, the development of ILCs and T cells seems to depend on a shared transcriptional network. For example, GATA3 and Tcf7, which play essential roles during T cell development, are also indispensable for the development of multiple ILC subsets. Bcl11b is another critical component of a T cell lineage fate-specifying transcriptional network. In this issue, Yu et al. and Walker et al. independently describe the role of Bcl11b in specifying ILC2 development. One would have expected that, similar to GATA3 and Tcf7, Bcl11b would be critical for the development of multiple ILC lineages. However, the two papers in this issue report that Bcl11b appears to be essential for ILC2 development only. Consequently , Bcl11b deficiency leads to impaired immune responses to either papain treatment, influenza virus infection (Yu et al.), or Nippostrongylus brasiliensis helminth infection, without affecting the ability of mice to clear bacterial Citrobacter rodentium infection (Walker et al.). The authors show that Bcl11b is expressed in mature ILC2s as well as in a subset of Id2 + common helper-like innate lymphoid progenitors (ChILPs); Walker et al. but not Yu et al. also show that a proportion of other mature ILC subsets, such as CCR6  ILC3s, express Bcl11b. The discrepancy in Bcl11b expression by mature ILC3s between these two studies has not been resolved. Nevertheless, the Bcl11b-expressing ChILPs only give rise to ILC2s but not other ILCs, suggesting that the previously identified ChILPs contain a mixture of distinct committed ILC progenitors. This is consistent with another report in Nature suggesting that within the ChILP compartment, the PLZF + progenitors are largely committed to specific ILC subsets and fail to generate lymphoid tissue inducers, which represent another subset of ChILP-derived ILCs. Both reports also show that Bcl11b-expressing ILC2 progenitors express high levels of GATA3. However, other studies have reported that GATA3 hi progenitors also give rise to other ILCs. In addition, GATA3 is constantly required for the maintenance of ILC2s, whereas inducible deletion of …