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Tertiary lymphoid organs are aggregates of immune and stromal cells including high endothelial venules and lymphatic vessels that resemble secondary lymphoid organs and can be induced at nonlymphoid sites during inflammation. The function of lymphatic vessels within tertiary lymphoid organs remains poorly understood. During lung transplant tolerance, [Foxp3.sup.+] cells accumulate in tertiary lymphoid organs that are induced within the pulmonary grafts and are critical for the local downregulation of alloimmune responses. Here, we showed that tolerant lung allografts could induce and maintain tolerance of heterotopic donor-matched hearts through pathways that were dependent on the continued presence of the transplanted lung. Using lung retransplantation, we showed that [Foxp3.sup.+] cells egressed from tolerant lung allografts via lymphatics and were recruited into donor-matched heart allografts. Indeed, survival of the heart allografts was dependent on lymphatic drainage from the tolerant lung allograft to the periphery. Thus, our work indicates that cellular trafficking from tertiary lymphoid organs regulates immune responses in the periphery. We propose that these findings have important implications for a variety of disease processes that are associated with the induction of tertiary lymphoid organs., Introduction Tertiary lymphoid organs can be induced in nonlymphoid tissues during states of chronic inflammation or antigen exposure and are structurally similar to secondary lymphoid organs. One such example is [...]

Abstract Background The GM2 gangliosidoses (GM2), Tay-Sachs and Sandhoff diseases, are rare, autosomal recessive genetic disorders caused by mutations in the lysosomal enzyme β-hexosaminidase A (HEXA) or β-hexosaminidase B (HEXB) genes, respectively. A minority of patients have a late-onset form of disease that presents from late-childhood to adulthood and has a slowly progressive course with prolonged survival. Little research has been published documenting patient experiences with late-onset Tay-Sachs and Sandhoff diseases and how the disease impacts their daily lives and functioning. This study explored the most frequent symptoms and functional impacts experienced by patients with late-onset GM2 gangliosidosis through interviews with patients and caregivers. Methods A qualitative research study design was employed, using three focus groups and 18 one-on-one interviews with patients who were recruited at the National Tay-Sachs and Allied Diseases Annual Family Conference. Transcripts were generated from the discussions, and patient quotes were analyzed using a content analysis approach. Concepts were aggregated into symptom and functional impacts, and the frequency of mention in the focus groups and individual interviews was calculated. Key findings Many of the frequently described symptoms [muscle weakness (n = 19, 95%), “clumsy” gait (n = 12, 60%), fatigue (n = 10, 50%)] and impacts [difficulty walking (n = 19, 95%), falling (n = 17, 85%), and climbing stairs (n = 16, 80%)] disclosed by patients and caregivers were similar to those previously reported in the literature. However, less frequently described symptoms such as gastrointestinal issues (n = 4, 20%) and coughing fits (n = 5, 25%) have been expanded upon. This study evaluated the immediate impact of these symptoms on the patients’ lives to highlight the burden of these symptoms and the functional limitations on daily living activities, independence, and emotional well-being. The findings were used to develop a conceptual disease model that could serve as a foundation for patient-centered outcomes in clinical trials and provide insights to the medical community that may benefit patient care. Conclusions This study contributes to the current understanding of symptoms associated with late-onset GM2 gangliosidosis, and further identifies the many consequences and impacts of the disease. These symptoms and impacts could be measured in clinical trials to examine the effects of novel treatments from the patient perspective.

Bronchiolitis obliterans syndrome (BOS) is a major impediment to lung transplant survival and is generally resistant to medical therapy. Extracorporeal photophoresis (ECP) is an immunomodulatory therapy that shows promise in stabilizing BOS patients, but its mechanisms of action are unclear. In a mouse lung transplant model, we show that ECP blunts alloimmune responses and inhibits BOS through lowering airway TGF-[beta] bioavailability without altering its expression. Surprisingly, ECP-treated leukocytes were primarily engulfed by alveolar macrophages (AMs), which were reprogrammed to become less responsive to TGF-[beta] and reduce TGF-[beta] bioavailability through secretion of the TGF-[beta] antagonist decorin. In untreated recipients, high airway TGF-[beta] activity stimulated AMs to express CCL2, leading to [CCR2.sup.+] monocyte-driven BOS development. Moreover, we found TGF-[beta] receptor 2-dependent differentiation of [CCR2.sup.+] monocytes was required for the generation of monocyte-derived AMs, which in turn promoted BOS by expanding tissue-resident memory CD8* T cells that inflicted airway injury through Blimp-1-mediated granzyme B expression. Thus, through studying the effects of ECP, we have identified an AM functional plasticity that controls a TGF-[beta]-dependent network that couples [CCR2.sup.+] monocyte recruitment and differentiation to alloimmunity and BOS., Introduction Bronchiolitis obliterans syndrome (BOS) is the most common form of chronic lung allograft dysfunction (CLAD) and the leading cause of rejection after the first year of transplantation (1). The [...]

Lymph node (LN) fibroblastic reticular cells (FRCs) define LN niches and regulate lymphocyte homeostasis through producing diverse extracellular matrix (ECM) components. We examined the role of ECM laminin [alpha]4 (Lama4) using FRC-Lama4 conditional KO Pdgfrb-[Cre.sup.-/-] * [Lama4.sup.fl/fl] mice. Single-cell RNA-sequencing (scRNA-Seq) data showed the promoter gene Pdgfrb was exclusively expressed in FRCs. Depleting FRC-Lama4 reduced Tregs and dendritic cells, decreased high endothelial venules, impaired the conduit system, and downregulated T cell survival factors in LNs. FRC-Lama4 depletion impaired the homing of lymphocytes to LNs in homeostasis and after allografting. Alloantigen-specific T cells proliferated, were activated to greater degrees in LNs lacking FRC-Lama4, and were more prone to differentiate into effector phenotypes relative to the Treg phenotype. In murine cardiac transplantation, tolerogenic immunosuppression was not effective in FRC-Lama4 recipients, which produced more alloantibodies than WT. After lung transplantation, FRC-Lama4-KO mice had more severe graft rejection with fewer Tregs in their LNs. Overall, FRC-Lama4 critically contributes to a tolerogenic LN niche by supporting T cell migration, constraining T cell activation and proliferation, and promoting Treg differentiation. Hence, it serves as a therapeutic target for immunoengineering., Introduction Mammalian lymph nodes (LNs) serve as the primary initiation sites of immune responses, acting by choreographing the interactions of T cells, B cells, macrophages, and dendritic cell (DCs). The [...]

Antibody-mediated rejection (AMR) is a principal cause of acute and chronic failure of lung allografts. However, mechanisms mediating this oftentimes fatal complication are poorly understood. Here, we show that [Foxp3.sup.+] T cells formed aggregates in rejection-free human lung grafts and accumulated within induced bronchus- associated lymphoid tissue (BALT) of tolerant mouse lungs. Using a retransplantation model, we show that selective depletion of graft-resident [Foxp3.sup.+] T lymphocytes resulted in the generation of donor-specific antibodies (DSA) and AMR, which was associated with complement deposition and destruction of airway epithelium. AMR was dependent on graft infiltration by B and T cells. Depletion of graft-resident [Foxp3.sup.+] T lymphocytes resulted in prolonged interactions between B and [CD4.sup.+] T cells within transplanted lungs, which was dependent on CXCR5-CXCL13. Blockade of CXCL13 as well as inhibition of the CD40 ligand and the ICOS ligand suppressed DSA production and prevented AMR. Thus, we have shown that regulatory [Foxp3.sup.+] T cells residing within BALT of tolerant pulmonary allografts function to suppress B cell activation, a finding that challenges the prevailing view that regulation of humoral responses occurs peripherally. As pulmonary AMR is largely refractory to current immunosuppression, our findings provide a platform for developing therapies that target local immune responses., Introduction Lung transplantation is the only treatment available for numerous patients suffering from end-stage pulmonary failure. Compared with outcomes for other organ transplants, that after lung transplantation remains far worse, [...]

A comprehensive compilation is provided of the medicinal plants of the Southeast Asian country of Myanmar (formerly Burma). This contribution, containing 123 families, 367 genera, and 472 species, was compiled from earlier treatments, monographs, books, and pamphlets, with some medicinal uses and preparations translated from Burmese to English. The entry for each species includes the Latin binomial, author(s), common Myanmar and English names, range, medicinal uses and preparations, and additional notes. Of the 472 species, 63 or 13% of them have been assessed for conservation status and are listed in the IUCN Red List of Threatened Species (IUCN 2017). Two species are listed as Extinct in the Wild, four as Threatened (two Endangered, two Vulnerable), two as Near Threatened, 48 Least Concerned, and seven Data Deficient. Botanic gardens worldwide hold 444 species (94%) within their living collections, while 28 species (6%) are not found any botanic garden. Preserving the traditional knowledge of Myanmar healers contributes to Target 13 of the Global Strategy for Plant Conservation.

Wendy Krupnick was born in Los Angeles, California, in 1953, and grew up in Crestwood Hills, a progressive, cooperative community in the Santa Monica Mountains. Over the past thirty-five years she has been involved in nearly every aspect of sustainable agriculture. Her oral history, conducted over the telephone by Ellen Farmer on August 15, 2007, provides a broad perspective on the evolution of this movement.Krupnick came to UC Santa Cruz as a transfer student from UC Santa Barbara in 1973 and majored in biology. She volunteered in the Chadwick Garden (under Steve Kaffka) as a student, and then returned in 1976-77 as an apprentice at the UC Santa Cruz Farm and Garden. Later she served as the garden coordinator for the Farallones Institute’s Integral Urban House in Berkeley and the Institute’s Rural Center in Sonoma County. At the same time, she worked with pioneering organic farmer Warren Weber at Star Route Farm in Bolinas, California. Through Weber, Krupnick joined the California Certified Organic Farmers (CCOF) and was the first secretary of that organization.Krupnick cultivated farm-restaurant connections in the Bay Area, collaborating with Rosalind Creasy on the book Cooking from the Garden, tending a restaurant garden where she grew produce for Jessie Ziff Cool’s Flea Street Cafe and Late for the Train restaurants on the San Francisco Peninsula, and helping organize the Tasting of Summer Produce festival at the Oakland Museum. Still later, Krupnick managed the trial garden and did outreach and marketing at Shepherd’s Garden Seeds in Felton, California. At the time this interview was conducted, she was coordinating the four-acre educational market garden for the Santa Rosa Junior College Sustainable Agriculture Program.