Background: Bcl6 is required for the development of T follicular helper and regulatory (Tfh, Tfr) cells that regulate germinal center responses. Bcl6 also impacts the function of regulatory T (Treg) cells. Objective:The goal of this study is to define the functions of Bcl6 in Treg cells including Tfr cells in the context of allergic airway inflammation (AAI). Methods: We employed a model of house dust mite (HDM) sensitization to challenge wild type, Bcl6 fl/fl Foxp3-Cre and Prdm1(Blimp1) fl/fl Foxp3-Cre mice to study the reciprocal roles of Bcl6 and Blimp1 in AAI. Results: In the HDM model, Tfr cells repress the production of IgE and Bcl6+ Treg cells suppress the generation of type 2 cytokine producing cells in the lungs. In mice with Bcl6deficient Treg cells, twice as many ST2 (IL-33R) + Tregs develop as observed in wild type mice. ST2 + Tregs in the context of AAI are Blimp1-dependent, express type 2 cytokines, and share features of visceral adipose tissue Treg cells. Bcl6-deficient Tregs are more susceptible, and Blimp1-deficient Tregs are resistant, to acquiring the ST2 + Treg cell phenotype in vitro and in vivo in response to IL-33. Bcl6-deficient ST2+ Tregs but not Bcl6-deficient ST2+ T conventional cells strongly promote AAI when transferred into recipient mice. Lastly, ST2 is required for the exacerbated AAI in Bcl6 fl/fl Foxp3-Cre mice. Conclusions: During AAI, Bcl6 and Blimp1 play dual roles in regulating Tfr activity in the germinal center and in the development of ST2 + Tregs that promote type 2 cytokine responses. Koh page 4 4 Key Messages: • Tfr cells limit IgE production in mice challenged by airway allergen • Bcl6 and Blimp1 reciprocally regulate ST2 + Treg development • ST2 + Tregs promote allergic airway inflammation Capsule Summary: Bcl6 attenuates allergic disease by promoting Tfr cell development to repress the allergen-specific humoral response and by limiting expansion of ST2 + Tregs.

T helper cell differentiation requires lineage-defining transcription factors and factors that have shared expression among multiple subsets. BATF is required for development of multiple Th subsets but functions in a lineage-specific manner. BATF is required for IL-9 production in Th9 cells but in contrast to its function as a pioneer factor in Th17 cells, BATF is neither sufficient nor required for accessibility at the Il9 locus. Here we show that STAT5 is the earliest factor binding and remodeling the Il9 locus to allow BATF binding in both mouse and human Th9 cultures. The ability of STAT5 to mediate accessibility for BATF is observed in other Th lineages and allows acquisition of the IL-9-secreting phenotype. STAT5 and BATF convert Th17 cells into cells that mediate IL-9-dependent effects in allergic airway inflammation and anti-tumor immunity. Thus, BATF requires the STAT5 signal to mediate plasticity at the Il9 locus.

Northern corn leaf blight, caused by the fungal pathogen Exserohilum turcicum, is a major disease of maize. The first major locus conferring resistance to E. turcicum race 0, Ht1, was identified over 50 years ago, but the underlying gene has remained unknown. We employed a map‐based cloning strategy to identify the Ht1 causal gene, which was found to be a coiled‐coil nucleotide‐binding, leucine‐rich repeat (NLR) gene, which we named PH4GP‐Ht1. Transgenic testing confirmed that introducing the native PH4GP‐Ht1 sequence to a susceptible maize variety resulted in resistance to E. turcicum race 0. A survey of the maize nested association mapping genomes revealed that susceptible Ht1 alleles had very low to no expression of the gene. Overexpression of the susceptible B73 allele, however, did not result in resistant plants, indicating that sequence variations may underlie the difference between resistant and susceptible phenotypes. Modelling of the PH4GP‐Ht1 protein indicated that it has structural homology to the Arabidopsis NLR resistance gene ZAR1, and probably forms a similar homopentamer structure following activation. RNA sequencing data from an infection time course revealed that 1 week after inoculation there was a threefold reduction in fungal biomass in the PH4GP‐Ht1 transgenic plants compared to wild‐type plants. Furthermore, PH4GP‐Ht1 transgenics had significantly more inoculation‐responsive differentially expressed genes than wild‐type plants, with enrichment seen in genes associated with both defence and photosynthesis. These results demonstrate that the NLR PH4GP‐Ht1 is the causal gene underlying Ht1, which represents a different mode of action compared to the previously reported wall‐associated kinase northern corn leaf blight resistance gene Htn1/Ht2/Ht3.

Plant pathogens cause significant crop loss worldwide, and new resistance genes deployed to combat diseases can be overcome quickly. Understanding the existing resistance gene diversity within the germplasm of major crops, such as maize, is crucial for the development of new disease‐resistant varieties. We analysed the nucleotide‐binding leucine‐rich repeat receptors (NLRs) of 26 recently sequenced diverse founder lines from the maize nested association mapping (NAM) population and compared them to the R gene complement present in a wild relative of maize, Zea luxurians. We found that NLRs in both species contain a large diversity of atypical integrated domains, including many domains that have not previously been found in the NLRs of other species. Additionally, the single Z. luxurians genome was found to have greater integrated atypical domain diversity than all 26 NAM founder lines combined, indicating that this species may represent a rich source of novel resistance genes. NLRs were also found to have very high sequence diversity and presence–absence variation among the NAM founder lines, with a large NLR cluster on Chr10 representing a diversity hotspot. Additionally, NLRs were shown to be mobile within maize genomes, with several putative interchromosomal translocations identified.