No abstract

Chronic muscle inflammation is a critical feature of Duchenne muscular dystrophy and contributes to muscle fibre injury and disease progression. Although previous studies have implicated T cells in the development of muscle fibrosis, little is known about their role during the early stages of muscular dystrophy. Here, we show that T cells are among the first cells to infiltrate mdx mouse dystrophic muscle, prior to the onset of necrosis, suggesting an important role in early disease pathogenesis. Based on our comprehensive analysis of the kinetics of the immune response, we further identify the early pre-necrotic stage of muscular dystrophy as the relevant time frame for T-cell-based interventions. We focused on protein kinase C θ (PKCθ, encoded by Prkcq), a critical regulator of effector T-cell activation, as a potential target to inhibit T-cell activity in dystrophic muscle. Lack of PKCθ not only reduced the frequency and number of infiltrating T cells but also led to quantitative and qualitative changes in the innate immune cell infiltrate in mdx/Prkcq muscle. These changes were due to the inhibition of T cells, since PKCθ was necessary for T-cell but not for myeloid cell infiltration of acutely injured muscle. Targeting T cells with a PKCθ inhibitor early in the disease process markedly diminished the size of the inflammatory cell infiltrate and resulted in reduced muscle damage. Moreover, diaphragm necrosis and fibrosis were also reduced following treatment. Overall, our findings identify the early T-cell infiltrate as a therapeutic target and highlight the potential of PKCθ inhibition as a therapeutic approach to muscular dystrophy. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

No abstract

Check the metadata sheet to make sure that the header information, especially author names and the corresponding affiliations are correctly shown. • Check the questions that may have arisen during copy editing and insert your answers/ corrections. • Check that the text is complete and that all figures, tables and their legends are included. Also check the accuracy of special characters, equations, and electronic supplementary material if applicable. If necessary refer to the Edited manuscript. • The publication of inaccurate data such as dosages and units can have serious consequences. Please take particular care that all such details are correct. • Please do not make changes that involve only matters of style. We have generally introduced forms that follow the journal's style. Substantial changes in content, e.g., new results, corrected values, title and authorship are not allowed without the approval of the responsible editor. In such a case, please contact the Editorial Office and return his/her consent together with the proof. • If we do not receive your corrections within 48 hours, we will send you a reminder. • Your article will be published Online First approximately one week after receipt of your corrected proofs. This is the official first publication citable with the DOI. Further changes are, therefore, not possible. • The printed version will follow in a forthcoming issue.

Several factors promote coloniality by enhancing the fitness of colony members. In birds, spatial proximity among nests, breeder abundance and reproductive synchrony have been proposed as primary factors responsible for enhanced colonial defence and foraging success, which, in turn, enhance reproductive success. Whether these factors function synergistically or antagonistically remains, however, an open question due to the absence of an integrated analysis of their effects on fitness. We studied a large population of the Lesser Kestrel, Falco naumanni, a facultative colonial species, breeding in colonies of different sizes in their typical pseudo-steppe habitat. We quantified both the singular and interactive effects of nest distance, breeder abundance and reproductive synchrony on kestrel fitness measured as the time to survival of eggs to hatching and nestlings to fledging. Egg survival increased as reproductive stages became more synchronous with the timing of colony breeding, whereas nestling survival benefited from a higher synchrony with most nests in the entire population. Nestling survival was also positively affected by the interaction between nest distance and breeder abundance. Our results suggest that the presence of additional breeders in the colony is not sufficient per se, to trigger colonial advantages, but instead, that synchronised reproduction among multiple breeding pairs nesting in close spatial proximity is necessary to realise those benefits. Our findings provide a novel perspective for future investigations that explore the mechanisms underlying fitness variation among Lesser Kestrel colonies and group-living species in genera

No abstract

No abstract

No abstract