Vapor-Induced Conversion of a Centrosymmetric Organic–Inorganic Hybrid Crystal into a Proton-Conducting Second-Harmonic-Generation-Active Material

Chemical responsivity in materials is essential to build systems with switchable functionalities. However, polarity-switchable materials are still rare because inducing a symmetry breaking of the crystal structure by adsorbing chemical species is difficult. In this study, we demonstrate that a molecular organic–inorganic hybrid crystal of (NEt4)2[MnN(CN)4] (1) undergoes polarity switching induced by water vapor and transforms into a rare example of proton-conducting second-harmonic-generation-active material. Centrosymmetric 1 transforms into noncentrosymmetric polar 1·3H2O and 1·MeOH by accommodating water and methanol molecules, respectively. However, only water vapor causes a spontaneous single-crystal-to-single-crystal transition. Moreover, 1·3H2O shows proton conduction with 2.3 × 10–6 S/cm at 298 K and a relative humidity of 80%

Interleukin-17 Induces an Atypical M2-Like Macrophage Subpopulation That Regulates Intestinal Inflammation

<div><p>Interleukin 17 (IL-17) is a pleiotropic cytokine that acts on both immune and non-immune cells and is generally implicated in inflammatory and autoimmune diseases. Although IL-17 as well as their source, mainly but not limited to Th17 cells, is also abundant in the inflamed intestine, the role of IL-17 in inflammatory bowel disease remains controversial. In the present study, by using IL-17 knockout (KO) mice, we investigated the role of IL-17 in colitis, with special focus on the macrophage subpopulations. Here we show that IL-17KO mice had increased susceptibility to DSS-induced colitis which was associated with decrease in expression of mRNAs implicated in M2 and/or wound healing macrophages, such as IL-10, IL-1 receptor antagonist, arginase 1, cyclooxygenase 2, and indoleamine 2,3-dioxygenase. Lamina propria leukocytes from inflamed colon of IL-17KO mice contained fewer CD11b⁺Ly6C⁺MHC Class II⁺ macrophages, which were derived, at least partly, from blood monocytes, as compared to those of WT mice. FACS-purified CD11b⁺ cells from WT mice, which were more abundant in Ly6C⁺MHC Class II⁺ cells, expressed increased levels of genes associated M2/wound healing macrophages and also M1/proinflammatory macrophages. Depletion of this population by topical administration of clodronate-liposome in the colon of WT mice resulted in the exacerbation of colitis. These results demonstrate that IL-17 confers protection against the development of severe colitis through the induction of an atypical M2-like macrophage subpopulation. Our findings reveal a previously unappreciated mechanism by which IL-17 exerts a protective function in colitis.</p></div

Aggravated DSS-induced colitis in IL-17KO mice is associated with reduced number of CD11b⁺Ly6C⁺MHC Class II⁺ macrophages in the inflamed colon.

<p>IL-17KO mice and WT controls were treated with DSS as described in the legend for <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0108494#pone-0108494-g001" target="_blank">Figure 1</a>. (A) LPLs were purified from pooled (n = 2–3) distal colon sections of untreated and DSS-treated mice and subjected to flow cytometry analysis. Gating strategy of live and CD45⁺ for CD11b⁺ cells was shown in upper panels. Representative data from seven independent experiments are shown. Number denotes frequency of gated cells. (B) The frequency of cells for each subset in A is shown. Graphs represent mean ± SEM of seven independent experiments. *p<0.05. (C) Representative flow cytometry profiles of cell surface molecules implicated in M2/anti-inflammatory macrophages on each subset depicted as in A. Gray histograms represent cells stained with isotype matched control mAbs.</p

CD11b⁺ cells from inflamed colonic LPLs of KO mice express significantly lower levels of genes implicated in M2/wound healing macrophages.

<p>IL-17KO mice and WT controls (n = 3) were treated with DSS as described in the legend for <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0108494#pone-0108494-g001" target="_blank">Figure 1</a>. Then, LPLs isolated from these mice were further purified into CD11b⁺ cell on FACS Aria, from which cDNA were prepared and subjected to real-time PCR analysis. Expression of target mRNA were normalized to the expression of β-actin mRNA for generation of ΔCt values, and relative mRNA expression was quantified with the ΔΔCt method. Data are expressed as mean ± SEM. *p<0.05; **p<0.01.</p

IL-17 deficient mice exhibit more severe acute colitis following DSS administration.

<p>IL-17KO mice and WT controls were given 1.5% DSS in drinking water or water alone for 7 days followed by consumption of water alone. Colitis severity was assessed by weight loss (A), colon length (day 10) (B) and H&E histology (day 0 and 10) (Calibration bar = 200 µm) (C). Colon barrier permeability was assessed on day 10 by detection of FITC-dextran serum (D). The results are expressed as mean values ± SEM for each geneotype in A (n = 5–6), B (n = 10), C (n = 2), and D (n = 5). *p<0.05; **p<0.01.</p

Blood monocytes are recruited into inflamed colons and differentiate into CD11b⁺Ly6C⁺MHC Class II⁺ macrophages in the presence of IL-17.

<p>Monocytes were purified from bone marrow of WT (CD45.1), WT (CD45.2) or IL-17KO (CD45.2), and adaptively transferred into WT (45.2), IL-17KO (CD45.2) or WT (CD45.1) mice (n = 3), respectively, followed by the treatment with DSS. On day 10, colonic LPLs were isolated from pooled colon, stained with anti-CD11b, anti-Ly6C, and anti-MHC Class II together with corresponding anti-CD45 congenic antibody, and subjected to flow cytometry analysis. A representative result from three independent experiments is shown.</p

Colonic expression of mRNA for genes involved in inflammation and anti-inflammation.

<p>IL-17KO mice and WT controls were treated with DSS as described in the legend for <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0108494#pone-0108494-g001" target="_blank">Figure 1</a>. Total RNA were purified from distal colon sections of untreated and DSS-treated individual mice (n = 3) and transcribed into cDNA, which were subsequently subjected for real-time PCR analysis. Expression of target mRNA were normalized to the expression of β-actin mRNA for generation of ΔCt values, and relative mRNA expression was quantified with the ΔΔCt method. Data are expressed as mean ± SEM. *p<0.05; **p<0.01.</p

Depletion of CD11b⁺Ly6C⁺MHC Class II⁺ macrophages accelerates colon inflammation in WT mice induced by DSS treatment.

<p>WT mice were given 1.5% DSS in drinking water for 7 days followed by consumption of water alone for another 3 days, during which the mice were treated with clodronate-liposome or control liposome intrarectally on days −1, 1, 3, and 5 as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0108494#s2" target="_blank">Materials and Methods</a>. (A) Representative FACS plots showing reduced CD11b⁺Ly6C⁺MHC Class II⁺ macrophages in colon of clodronate-liposome treated mice. (B) Changes in body weight over time were expressed as a percentage of the original weight. Data represent as mean ± SEM. The experiments were repeated two times with at least three mice per group per experiment.</p