Stromal Fibroblasts in Tertiary Lymphoid Structures: A Novel Target in Chronic Inflammation

Tertiary lymphoid structures (TLS) are organized aggregates of lymphocytes, myeloid, and stromal cells that provide ectopic hubs for acquired immune responses. TLS share phenotypical and functional features with secondary lymphoid organs (SLO); however, they require persistent inflammatory signals to arise and are often observed at target sites of autoimmune disease, chronic infection, cancer, and organ transplantation. Over the past 10 years, important progress has been made in our understanding of the role of stromal fibroblasts in SLO development, organization, and function. A complex and stereotyped series of events regulate fibroblast differentiation from embryonic life in SLOs to lymphoid organ architecture observed in adults. In contrast, TLS-associated fibroblasts differentiate from postnatal, locally activated mesenchyme, predominantly in settings of inflammation and persistent antigen presentation. Therefore, there are critical differences in the cellular and molecular requirements that regulate SLO versus TLS development that ultimately impact on stromal and hematopoietic cell function. These differences may contribute to the pathogenic nature of TLS in the context of chronic inflammation and malignant transformation and offer a window of opportunity for therapeutic interventions in TLS associated pathologies

Bimodal expansion of the lymphatic vessels is regulated by the sequential expression of IL-7 and lymphotoxin α1β2 in newly formed tertiary lymphoid structures

Lymphangiogenesis associated with tertiary lymphoid structure (TLS) has been reported in numerous studies. However, the kinetics and dynamic changes occurring to the lymphatic vascular network during TLS development have not been studied. Using a viralinduced, resolving model of TLS formation in the salivary glands of adult mice we demonstrate that the expansion of the lymphatic vascular network is tightly regulated. Lymphatic vessel expansion occurs in two distinct phases. The first wave of expansion is dependent on IL-7. The second phase, responsible for leukocyte exit from the glands, is regulated by lymphotoxin (LT)bR signaling. These findings, while highlighting the tight regulation of the lymphatic response to inflammation, suggest that targeting the LTa1b2/LTbR pathway in TLS-associated pathologies might impair a natural proresolving mechanism for lymphocyte exit from the tissues and account for the failure of therapeutic strategies that target these molecules in diseases such as rheumatoid arthritis

Hahn-Steinthal fracture: a case report

Isolated fracture of the capitellum is rare. We present clinical and radiological data on a single case of a fracture of capitellum. We came across a 31 year old woman who sustained an isolated Hahn Steinthal type of fracture. It was treated operatively by open reduction and internal fixation using mini fragment screws. The elbow was immobilized for 4 weeks. The patient regained full range of movement at 12 weeks post operatively. We reiterate that anatomical reduction and fixation is the right way to treat this injury

Ernest Renan's Race Problem

This review revisits the role of race in Ernest Renan's thought by situating contemporary debates in a long perspective that extends back to his texts and their earliest interpreters. Renan is an ambivalent figure: from the 1850s onwards he used ‘race’ to denote firm differences between the ‘Aryan’ and ‘Semitic’ language groups in history; but after 1870, he repeatedly condemned biological racism in various venues and contexts. I show that the tension between these two sides of Renan's thought has continually resurfaced in criticism and historiography ever since the late nineteenth century. Renan's racial views have been subject to particularly close scrutiny following Léon Poliakov's and Edward Said's critiques in the 1970s, but the ensuing debate risks developing into an inconclusive tug-of-war between attack and apologia. I propose three fresh directions for research. First, historians should situate the evolution of Renan's ideas on race in closer biographical context; secondly, they must reconsider the cultural authority of his texts, which is often more asserted than proven; thirdly, they should pay greater attention to his reception outside Europe, particularly regarding his writing on Islam