The active form of vitamin D (calcitriol) promotes CXCR5 expression during follicular helper T cell differentiation.

Follicular helper T (Tfh) cells promote B cell differentiation and antibody production in the B cell follicles of secondary lymphoid organs. Tfh cells express their signature transcription factor BCL6, interleukin (IL)-21, and surface molecules including inducible T cell costimulator, programmed cell death-1 (PD-1), and the chemokine receptor CXCR5. Migration of Tfh cells to B cell follicles largely depends on the CXCR5 expression induced by interactions with antigen-presenting dendritic cells in the T cell area. How Tfh cells acquire sufficient levels of CXCR5 expression, however, has remained unclear. Using our in vitro culture system to generate CXCR5low Tfh-like cells from naïve CD4+ T cells with IL-6 in the absence of other cell types, we found that the active form of vitamin D, calcitriol, markedly enhanced CXCR5 expression after the release from persistent T cell receptor (TCR) stimulation. CH-223191, an aryl hydrocarbon receptor antagonist, further enhanced CXCR5 expression. IL-12 but not IL-4, in place of IL-6, also supported calcitriol to enhance CXCR5 expression even before the release from TCR stimulation, whereas the cell viability sharply decreased after the release. The Tfh-like cells generated with IL-6 and calcitriol exhibited chemotaxis towards CXCL13, expressed IL-21, and helped B cells to produce IgG antibodies in vitro more efficiently than Tfh-like cells generated without added calcitriol. Calcitriol injections into antigen-primed mice increased the proportion of CXCR5+PD-1+CD4+ cells in their lymphoid organs, and enhanced T cell entry into B-cell follicles. These results suggest that calcitriol promotes CXCR5 expression in developing Tfh cells and regulates their functional differentiation.

[2,7-Dimeth-oxy-8-(4-meth-oxy-benzo-yl)naphthalen-1-yl](4-meth-oxy-phen-yl)methanone chloro-form monosolvate.

In the title compound, C28H24O6·CHCl3, the two 4-meth-oxy-benzoyl groups at the 1- and 8-positions of the naphthalene ring system are aligned almost anti-parallel, the benzene rings making a dihedral angle of 25.76 (7)°. The naphthalene ring system makes dihedral angles of 72.51 (7) and 73.33 (7)° with the benzene rings. In the crystal, the naphthalene mol-ecules are linked by C-H⋯O inter-actions, forming a helical chain along the b-axis direction. A C-H⋯Cl inter-action is also observed between the aroylated naphthalene and chloro-form mol-ecules. The chloro-form mol-ecule is disordered over two positions with site occupancies of 0.478 (5) and 0.522 (5).

(2,7-Dimeth-oxy-naphthalen-1-yl)(4-meth-oxy-phen-yl)methanone.

In the mol-ecule of the title compound, C20H18O4, the dihedral angle between the naphthalene ring system and the benzene ring is 81.74 (5)°. An inter-molecular C-H⋯O inter-action is formed between an H atom at the 6-position of the naphthalene ring and the O atom of the meth-oxy group at the 7-position.

(8-Benzoyl-2,7-dimeth-oxy-naphthalen-1-yl)(4-phen-oxy-phen-yl)methanone.

In the mol-ecule of the title compound, C32H24O5, the benzoyl group and the 4-phenoxy substituted benzoyl group at the 1- and 8-positions of the naphthalene ring system are aligned almost anti-parallel. The two benzene rings make a dihedral angle of 21.18 (10)°, and are inclined to the naphthalene ring system by 86.53 (9) and 82.95 (8)°, respectively. In the crystal, C-H⋯O inter-actions are observed involving aromatic and meth-oxy H atoms with ketonic carbonyl O atoms, as well as C-H⋯π inter-actions between aromatic H atoms and the π-systems of naphthalene and benzene rings. These interactions form a three-dimensional architecture and afford a waved alignment of the naphthalene ring systems along the c axis.

(2,7-Dimeth-oxy-naphthalen-1-yl)(4-phen-oxy-phen-yl)methanone.

In the title mol-ecule, C25H20O4, the naphthalene and phen-oxy groups are oriented nearly perpendicular with respect to the benzene ring of the benzoyl group, with dihedral angles of 89.61 (5) and 86.13 (6)°, respectively. The crystal structure features C-H⋯O and C-H⋯π inter-actions.

1-Benzoyl-naphthalene-2,7-diyl dibenzoate.

In the title compound, C(31)H(20)O(5), the phenyl rings of the benzo-yloxy and benzoyl groups are twisted away from the naphthalene ring system by 64.27 (6), 73.62 (5) and 80.41 (6)°. In the crystal, C-H⋯O hydrogen bonds and C-H⋯π inter-actions link the mol-ecules, forming tubular chains parallel to the b axis. The chains are further connected into a three-dimensional network by C-H⋯π inter-actions and π-π stacking contacts [centroid-centroid distances = 3.622 (10)-3.866 (12) Å].

(4-Eth-oxy-benzo-yl)[8-(4-eth-oxy-benzo-yl)-2,7-di-meth-oxy-naphthalen-1-yl]methanone.

The title mol-ecule, C30H28O6, possesses crystallographically imposed twofold symmetry, with two central C atoms in the naphthalene unit lying on the rotation axis along [001]. The 4-eth-oxy-benzoyl groups at the peri positions of the naphthalene ring system are disordered over two sets of sites with occupancies of 0.769 (4) and 0.231 (4). They are directed in opposite directions from the naphthalene plane (anti orientation). For the major component, the dihedral angle between the aroyl benzene ring and the naphthalene ring system is 75.62 (13)° [minor component 75.5 (4)°], and that between the aroyl benzene rings is 32.58 (15)°. In the crystal, mol-ecules are linked via C-H⋯O and C-H⋯π inter-actions, forming a three-dimensional network.

1,8-Bis(4-fluoro-benzo-yl)naphthalen-2,7-diyl dimethane-sulfonate.

The mol-ecule of the title compound, C26H18F2O8S2, lies across a crystallographic twofold rotation axis. The benzene rings of the 4-fluorobenzoyl groups make dihedral angles of 78.93 (12)° with the naphthalene ring system. An intra-molecular C-H⋯π inter-action occurs. In the crystal, a number of C-H⋯O inter-actions link the mol-ecules, forming a three-dimensional structure.

Bis(1-benzoyl-7-meth-oxy-naphthalen-2-yl) terephthalate.

The title molecule, C44H30O8, lies about a crystallographic inversion centre located at the centre of the central benzene ring. The benzene rings in the benzoyl and the terephthalate units make dihedral angles of 67.05 (7)° and 57.57 (7)°, respectively, with the naphthalene ring system. There is an intra-molecular C-H⋯O inter-action between the ketonic carbonyl O atom and an H atom on the naphthalene ring system. In the crystal, C-H⋯O inter-action of the benzene ring in the benzoyl group and weak C=O⋯π inter-action [O⋯centroid = 3.375 (2) Å] of the naphthalene ring with the O atom in the ketonic carbonyl group are observed. These inter-actions form layers parallel to the bc plane.

Release from persistent T cell receptor engagement and blockade of aryl hydrocarbon receptor activity enhance IL-6-dependent mouse follicular helper T-like cell differentiation in vitro.

Follicular helper T (Tfh) cells are crucial for humoral immunity. Dysregulation of Tfh cell differentiation can cause infectious, allergic, and autoimmune diseases. To elucidate the molecular mechanisms underlying Tfh cell differentiation, we attempted to establish an in vitro mouse model of Tfh cell differentiation in the absence of other cell types. Various cytokines and cell surface molecules are suggested to contribute to the differentiation. We found that stimulating naïve CD4+ T cells with immobilized antibodies to CD3, ICOS, and LFA-1 in the presence of soluble anti-CD28 antibody, IL-6, and antibodies that block IL-2 signaling for 3 days induced the expression of Bcl6 and Rorc(γt), master regulator genes of Tfh and Th17 cells, respectively. TGF-ß significantly enhanced cell proliferation and Bcl6 and Rorc(γt) expression. An additional 2 days of culture without immobilized antibodies selectively downregulated Rorc(γt) expression. These cells produced IL-21 and promoted B cells to produce IgG antibodies. Adding the aryl hydrocarbon receptor (AhR) antagonist CH-223191 to the T cell culture further downregulated Rorc(γt) expression without significantly affecting Bcl6 expression, and upregulated expression of a key Tfh marker, CXCR5. Although their CXCR5 expression levels were still not high, the CH-223191-treated cells showed chemotactic activity towards the CXCR5 ligand CXCL13. On the other hand, AhR agonists upregulated Rorc(γt) expression and downregulated CXCR5 expression. These findings suggest that AhR activity and the duration of T cell receptor stimulation contribute to regulating the balance between Tfh and Th17 cell differentiation. Although this in vitro system needs to be further improved, it may be useful for elucidating the mechanisms of Tfh cell differentiation as well as for screening physiological or pharmacological factors that affect Tfh cell differentiation including CXCR5 expression.

1,8-Dibenzoyl-naph-tha-lene-2,7-diyl dibenzoate.

In the title compound, C(38)H(24)O(6), the phenyl rings of the benzoyl and benzo-yloxy groups make dihedral angles of 67.12 (5), 85.15 (5), 76.41 (5) and 71.47 (5)° with the naphthal-ene ring system. In the crystal, C-H⋯O hydrogen bonds link mol-ecules into chains parallel to the b axis. The structure also features C-H⋯π and π-π stacking inter-actions, with centroid-centroid distances in the range 3.6441 (7)-3.9197 (8) Å.

[2,7-Dimeth-oxy-8-(4-propyl-benzo-yl)naphthalen-1-yl](4-propyl-phen-yl)methanone.

In the title compound, C(32)H(32)O(4), the 4-propyl-benzoyl groups at the 1- and 8-positions of the naphthalene ring system are aligned almost anti-parallel, and their benzene rings make a dihedral angle of 8.64 (10)°. The dihedral angles between the naphthalene ring system and the benzene rings are 69.37 (8) and 69.45 (8)°. In the crystal, C-H⋯O inter-actions link adjacent mol-ecules via their aroyl groups.

{2,7-Dimeth-oxy-8-[4-(2-methyl-prop-yl)benzo-yl]naphthalen-1-yl}[4-(2-methyl-prop-yl)phen-yl]methanone.

In the mol-ecule of the title compound, C34H36O4, the two 4-isobutyl-benzoyl groups at the 1- and 8-positions of the naphthalene ring system are aligned almost anti-parallel, and the benzene rings make a dihedral angle of 21.59 (7)°. The dihedral angles between the benzene rings and the naphthalene ring system are 69.26 (6) and 64.29 (5)°. There are no classical hydrogen bonds in the structure, but inversion-related mol-ecules engage in π-π stacking, with an inter-planar spacing between related naphthalene groups of 3.4120 (16) Å.

[Can industrial laundry remove Bacillus cereus from hospital linen?].

Contaminated hospital linen has caused some cases of Bacillus cereus bacteremia in Japan. We analyzed the disinfection efficacy of industrial washing of hospital towels and sheets by counting the number of B. cereus on linen before and after washing. That before washing averaged 7.6 cells/cm2 on unwashed sheets, decreasing to 1.2 cells/cm2 after washing. That on unwashed towels, however, averaged 10(6) cells/cm2 before washing and 1096 cells/cm2 after washing, which was very high and suggested the possibility of causing nosocomial infection.