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Interaction among various adaptive, circulating cells and tissue-resident cells including innate lymphocytes during the establishment and maintenance of the barrier-tissue immune system has only recently started to be explored. Here, we show that the cellular crosstalk with circulating T cells and other resident cells regulated the population size of type 2 innate lymphoid cells (ILC2s) in the small intestine lamina propria. Rag1

Staphylococcal superantigen-like (SSL) protein is a family of exotoxins that consists of 14 SSLs, and the roles of several SSLs in immune evasion of the cocci have been revealed. However little is known whether they act as immune activators and are involved in inflammatory disorders such as atopic dermatitis. In this study we examined whether SSLs activate mast cells, the key player of local inflammation. SSL12 evoked the release of a granule enzyme β-hexosaminidase from bone marrow derived mast cells (BMMCs) in the absence of IgE. The release of the granule enzyme caused by SSL12 was not accompanied with the leakage of a cytosolic enzyme lactate dehydrogenase (LDH), unlike staphylococcal δ-toxin that was reported to induce both the release of β-hexosaminidase and the leakage of LDH from the cells, suggesting that SSL12 evokes the degranulation of mast cells without cell membrane damage. Furthermore SSL12 induced IL-6 and IL-13 in both mRNA and protein levels indicating that SSL12 induces de novo synthesis of the cytokines. Evans blue extravasation was elevated by the intradermal injection of SSL12, suggesting that SSL12 is also able to evoke local inflammation in vivo. These findings indicate the novel mast cell activating activity of SSLs, and SSL12 is likely an important factor in both initiation phase and effector phase of allergic and immune responses.

TAK1 (encoded by Map3k7 ) is a mitogen-activated protein kinase kinase kinase (MAP3K), which activates the transcription factors AP-1 and NF-κB in response to receptor activator of NF-κB ligand (RANKL) stimulation, thus constituting a key regulator of osteoclast differentiation. Here we report the functional relevance of the kinase activity of TAK1 in the late stage of osteoclast differentiation in vivo using Ctsk -Cre mice and TAK1 mutant mice in which the TAK1 kinase domain was flanked by loxP. The Map3k7 flox/kd Ctsk Cre/+ mice displayed a severe osteopetrotic phenotype due to a marked decrease in osteoclast number. RANKL-induced activation of MAPK and NF-κB was impaired in the late stage of osteoclast differentiation. The absence of suppressive effect of an administered NF-κB inhibitor on the late stage of osteoclastogenesis led us to investigate unknown TAK1 targets in osteoclast differentiation. We performed a phosphoproteomic analysis of RANKL-stimulated osteoclast precursor cells from Map3k7 flox/kd Ctsk Cre/+ mice, revealing multiple targets regulated by TAK1 during osteoclastogenesis. Thus, TAK1 functions as a critical regulator of the phosophorylation status of various cellular proteins that govern osteoclastogenesis.