HLA-DP on Epithelial Cells Enables Tissue Damage by NKp44+ Natural Killer Cells in Ulcerative Colitis

Background & aims: Ulcerative colitis (UC) is characterized by severe inflammation and destruction of the intestinal epithelium, and is associated with specific risk single nucleotide polymorphisms in HLA class II. Given the recently discovered interactions between subsets of HLA-DP molecules and the activating natural killer (NK) cell receptor NKp44, genetic associations of UC and HLA-DP haplotypes and their functional implications were investigated.Methods: HLA-DP haplotype and UC risk association analyses were performed (UC: n = 13,927; control: n = 26,764). Expression levels of HLA-DP on intestinal epithelial cells (IECs) in individuals with and without UC were quantified. Human intestinal 3-dimensional (3D) organoid cocultures with human NK cells were used to determine functional consequences of interactions between HLA-DP and NKp44.Results: These studies identified HLA-DPA1∗01:03-DPB1∗04:01 (HLA-DP401) as a risk haplotype and HLA-DPA1∗01:03-DPB1∗03:01 (HLA-DP301) as a protective haplotype for UC in European populations. HLA-DP expression was significantly higher on IECs of individuals with UC compared with controls. IECs in human intestinal 3D organoids derived from HLA-DP401pos individuals showed significantly stronger binding of NKp44 compared with HLA-DP301pos IECs. HLA-DP401pos IECs in organoids triggered increased degranulation and tumor necrosis factor production by NKp44+ NK cells in cocultures, resulting in enhanced epithelial cell death compared with HLA-DP301pos organoids. Blocking of HLA-DP401-NKp44 interactions (anti-NKp44) abrogated NK cell activity in cocultures.Conclusions: We identified an UC risk HLA-DP haplotype that engages NKp44 and activates NKp44+ NK cells, mediating damage to intestinal epithelial cells in an HLA-DP haplotype-dependent manner. The molecular interaction between NKp44 and HLA-DP401 in UC can be targeted by therapeutic interventions to reduce NKp44+ NK cell-mediated destruction of the intestinal epithelium in UC

Supernova 2002bo: inadequacy of the single parameter description

We present optical/near-infrared photometry and spectra of the type Ia SN 2002bo spanning epochs from -13 days before maximum B-band light to +102 days after. The pre-maximum optical coverage is particularly complete. In some respects, SN 2002bo behaves as a typical "Branch normal" type Ia supernova (SN Ia) at optical and IR wavelengths. We find a B-band risetime of 17.9+-0.5 days, a Dm_{15}(B) of 1.13+-0.05, and a M_B=-19.41+-0.42. However, comparison with other type Ia supernovae having similar Delta m_{15}(B) values indicates that in other respects SN 2002bo is unusual. While the optical spectra of SN 2002bo are very similar to those of SN 1984A, lower velocities and a generally more structured appearance are found in SNe 1990N, 1994D and 1998bu. For supernovae having Dm_(15)(B) > 1.2, we confirm the variation of R(SiII) (Nugent et al. 1995) with Dm_(15)(B). However, for supernovae such as SN2002bo, with lower values of Dm_(15)(B) the relation breaks down. Moreover, the evolution of R(SiII) for SN 2002bo is strikingly different from that shown by other type Ia supernovae. The velocities of SN 2002bo and 1984A derived from SII 5640A, SiII 6355A and CaII H&K lines are either much higher and/or evolve differently from those seen in other normal SNe Ia events. We suggest that the unusually low temperature, the presence of high-velocity intermediate-mass elements and the low abundance of carbon at early times indicates that burning to Si penetrated to much higher layers than in more normal type Ia supernovae. This may be indicative of a delayed-detonation explosion.Comment: Accepted to MNRAS. Some near-IR photometry has been added. The paper can be retrieved also at http://web.pd.astro.it/supern/ps/sn02bo_v17_mn2.ps.g

2MASS J0516288+260738: Discovery of the first eclipsing late K + Brown dwarf binary system

Original article available at: http://www.aanda.org/--Copyright The European Southern Observatory DOI : 10.1051/0004-6361:20031241We report the discovery of a new eclipsing system less than one arcminute south of the pulsating DB white dwarf KUV05134+2605. The object could be identified with the point source 2MASSJ0516288+260738 published by the Two Micron All Sky Survey.We present and discuss the first light curves as well as some additional colour and spectral information. The eclipse period of the system is 1.29 d, and, assuming this to be identical to the orbital period, the best light curve solution yields a mass ratio of m2/m1 = 0.11, a radius ratio of r2/r1 ≈ 1 and an inclination of 74◦. The spectral anaylsis results in a Teff = 4200 K for the primary. On this basis, we suggest that the new system probably consists of a late K + Brown dwarf (which would imply a system considerably younger than ≈0.01 Gyr to have r2/r1 ≈ 1), and outline possible future observations.Peer reviewe

CXCR5+PD-1++ CD4+ T cells colonize infant intestines early in life and promote B cell maturation

Gastrointestinal infections are a major cause for serious clinical complications in infants. The induction of antibody responses by B cells is critical for protective immunity against infections and requires CXCR5+PD-1++ CD4+ T cells (TFH cells). We investigated the ontogeny of CXCR5+PD-1++ CD4+ T cells in human intestines. While CXCR5+PD-1++ CD4+ T cells were absent in fetal intestines, CXCR5+PD-1++ CD4+ T cells increased after birth and were abundant in infant intestines, resulting in significant higher numbers compared to adults. These findings were supported by scRNAseq analyses, showing increased frequencies of CD4+ T cells with a TFH gene signature in infant intestines compared to blood. Co-cultures of autologous infant intestinal CXCR5+PD-1+/−CD4+ T cells with B cells further demonstrated that infant intestinal TFH cells were able to effectively promote class switching and antibody production by B cells. Taken together, we demonstrate that functional TFH cells are numerous in infant intestines, making them a promising target for oral pediatric vaccine strategies