Highlights d PD-1 is upregulated on ILC2s in adipose tissue of obese mice d PD-1 expression is increased in a TNF-and IL-33-dependent manner d PD-1 correlates with impaired ILC2 function in the presence of PD-L1 + macrophages d PD-1 blockade ameliorates glucose tolerance and adaptation to environmental cold

Idiopathic pulmonary fibrosis is a progressive, devastating, and yet untreatable fibrotic disease of unknown origin. Interleukin-33 (IL-33), an IL-1 family member acts as an alarmin with pro-inflammatory properties when released after stress or cell death. Here, we investigated the role of IL-33 in the bleomycin (BLM)-induced inflammation and fibrosis model using mice IL-33 receptor [chain suppression of tumorigenicity 2 (ST2)] mice compared with C57BL/6 wild-type mice. Unexpectedly, 24 h post-BLM treatment ST2-deficient mice displayed augmented inflammatory cell recruitment, in particular by neutrophils, together with enhanced levels of chemokines and remodeling factors in the bronchoalveolar space and/or the lungs. At 11 days, lung remodeling and fibrosis were decreased with reduced M2 macrophages in the lung associated with M2-like cytokine profile in ST2-deficient mice, while lung cellular inflammation was decreased but with fluid retention (edema) increased. In vivo magnetic resonance imaging (MRI) analysis demonstrates a rapid development of edema detectable at day 7, which was increased in the absence of ST2. Our results demonstrate that acute neutrophilic pulmonary inflammation leads to the development of an IL-33/ST2-dependent lung fibrosis associated with the production of M2-like polarization. In addition, non-invasive MRI revealed enhanced inflammation with lung edema during the development of pulmonary inflammation and fibrosis in absence of ST2.

The microvessels of the rat subfornical organ (SFO) are heterogeneous: those of the caudal part lack a blood-brain barrier (BBB) unlike those of the rostral part. The astroglial environment of these microvessels has been studied by combining an immunocytochemical technique employing an anti-GFAP (glial fibrillary acidic protein) antiserum with the morphological detection of a barrier to the protein-silver complex. All the SFO microvessels are surrounded by astrocytes characterized by a tumescent aspect; however, the relative proximity between the astrocytic feet and the endothelial cells varies considerably. The capillaries provided with a barrier (rostral SFO) are contiguous with the astrocytes from which they are only separated by a basement membrane. The capillaries devoid of BBB (caudal SFO) are surrounded by a pericapillary space that keeps the astrocytes at a short distance (capillaries with a very rich vesicular endothelium) or at a long distance (capillaries with a fenestrated endothelium). The astrocytes are absent in the choroid plexus where all microvessels are fenestrated and lack a barrier. These data suggest that the astrocytes release one or more signals which in their vicinity inhibit the expression of endothelial morphological characteristics (fenestrations, vesicles) responsible for the leakage of plasmatic proteins from the blood to the cerebral parenchyma of the circumventricular organs.