Several wall-associated kinases participate positively and negatively in basal defense against rice blast fungus.

BACKGROUND: Receptor-like kinases are well-known to play key roles in disease resistance. Among them, the Wall-associated kinases (WAKs) have been shown to be positive regulators of fungal disease resistance in several plant species. WAK genes are often transcriptionally regulated during infection but the pathways involved in this regulation are not known. In rice, the OsWAK gene family is significantly amplified compared to Arabidopsis. The possibility that several WAKs participate in different ways to basal defense has not been addressed. Moreover, the direct requirement of rice OSWAK genes in regulating defense has not been explored. RESULTS: Here we show using rice (Oryza sativa) loss-of-function mutants of four selected OsWAK genes, that individual OsWAKs are required for quantitative resistance to the rice blast fungus, Magnaporthe oryzae. While OsWAK14, OsWAK91 and OsWAK92 positively regulate quantitative resistance, OsWAK112d is a negative regulator of blast resistance. In addition, we show that the very early transcriptional regulation of the rice OsWAK genes is triggered by chitin and is partially under the control of the chitin receptor CEBiP. Finally, we show that OsWAK91 is required for H2O2 production and sufficient to enhance defense gene expression during infection. CONCLUSIONS: We conclude that the rice OsWAK genes studied are part of basal defense response, potentially mediated by chitin from fungal cell walls. This work also shows that some OsWAKs, like OsWAK112d, may act as negative regulators of disease resistance

The THAP–zinc finger protein THAP1 regulates endothelial cell proliferation through modulation of pRB/E2F cell-cycle target genes

AbstractWe recently cloned a novel human nuclear factor (designated THAP1) from postcapillary venule endothelial cells (ECs) that contains a DNA-binding THAP domain, shared with zebrafish E2F6 and several Caenorhabditis elegans proteins interacting genetically with retinoblastoma gene product (pRB). Here, we show that THAP1 is a physiologic regulator of EC proliferation and cell-cycle progression, 2 essential processes for angiogenesis. Retroviral-mediated gene transfer of THAP1 into primary human ECs inhibited proliferation, and large-scale expression profiling with microarrays revealed that THAP1-mediated growth inhibition is due to coordinated repression of pRB/E2F cell-cycle target genes. Silencing of endogenous THAP1 through RNA interference similarly inhibited EC proliferation and G1/S cell-cycle progression, and resulted in down-regulation of several pRB/E2F cell-cycle target genes, including RRM1, a gene required for S-phase DNA synthesis. Chromatin immunoprecipitation assays in proliferating ECs showed that endogenous THAP1 associates in vivo with a consensus THAP1-binding site found in the RRM1 promoter, indicating that RRM1 is a direct transcriptional target of THAP1. The similar phenotypes observed after THAP1 overexpression and silencing suggest that an optimal range of THAP1 expression is essential for EC proliferation. Together, these data provide the first links in mammals among THAP proteins, cell proliferation, and pRB/E2F cell-cycle pathways

IL-33, an Alarmin of the IL-1 Family Involved in Allergic and Non Allergic Inflammation: Focus on the Mechanisms of Regulation of Its Activity

Interleukin-33 (IL-33) is a member of the interleukin-1 (IL-1) family that is expressed in the nuclei of endothelial and epithelial cells of barrier tissues, among others. It functions as an alarm signal that is released upon tissue or cellular injury. IL-33 plays a central role in the initiation and amplification of type 2 innate immune responses and allergic inflammation by activating various target cells expressing its ST2 receptor, including mast cells and type 2 innate lymphoid cells. Depending on the tissue environment, IL-33 plays a wide variety of roles in parasitic and viral host defense, tissue repair and homeostasis. IL-33 has evolved a variety of sophisticated regulatory mechanisms to control its activity, including nuclear sequestration and proteolytic processing. It is involved in many diseases, including allergic, inflammatory and infectious diseases, and is a promising therapeutic target for the treatment of severe asthma. In this review, I will summarize the literature around this fascinating pleiotropic cytokine. In the first part, I will describe the basics of IL-33, from the discovery of interleukin-33 to its function, including its expression, release and signaling pathway. The second part will be devoted to the regulation of IL-33 protein leading to its activation or inactivation

Interleukin-33 (IL-33): A nuclear cytokine from the IL-1 family

International audienc

Innate lymphoid cells in asthmatic patients

International audienc

L' interleukine-33, cytokine de la famille IL-1 (régulation par les protéases inflammatoires)

TOULOUSE3-BU Sciences (315552104) / SudocSudocFranceF

L’interleukine 33

L’interleukine-33 est une cytokine nucléaire de la famille de l’IL-1, exprimée par les cellules endothéliales et épithéliales des tissus en contact avec l’environnement. Elle est libérée lors de dommages tissulaires et joue le rôle d’alarmine en prévenant le système immunitaire d’un danger. Elle est impliquée dans l’immunité innée de type-2 et l’inflammation allergique, mais des études récentes suggèrent qu’elle peut, selon le contexte environnemental, jouer d’autres rôles dans l’homéostasie ou l’immunité antivirale, par exemple. Elle est associée à de nombreuses pathologies, notamment allergiques, inflammatoires ou infectieuses, et pourrait être une cible thérapeutique de choix pour le traitement de l’asthme sévère

L’interleukine 33

International audienc

Molecular mimicry between IL-33 and KSHV for attachment to chromatin through the H2A–H2B acidic pocket

Interleukin-33 (IL-33) is an IL-1-like ligand for the ST2 receptor that stimulates the production of Th2-associated cytokines. Recently, we showed that IL-33 is a chromatin-associated factor in the nucleus of endothelial cells in vivo. Here, we report the identification of a short IL-33 chromatin-binding peptide that shares striking similarities with a motif found in Kaposi sarcoma herpesvirus LANA (latency-associated nuclear antigen), which is responsible for the attachment of viral genomes to mitotic chromosomes. Similar to LANA, the IL-33 peptide docks into the acidic pocket formed by the H2A–H2B dimer at the nucleosomal surface and regulates chromatin compaction by promoting nucleosome–nucleosome interactions. Taken together, our data provide important new insights into the nuclear roles of IL-33, and show a unique example of molecular mimicry of a chromatin-associated cytokine by a DNA tumour virus. In addition, the data provide, to the best of our knowledge, the first demonstration of the existence of non-histone cellular factors that bind to the acidic pocket of the nucleosome