Acute Fulminant Colitis Caused by Idiopathic Mesenteric Inflammatory Veno-Occlusive Disease

Mesenteric inflammatory veno-occlusive disease (MIVOD) is an uncommon but important cause of bowel inflammation. MIVOD is characterised by lymphocytic inflammation and non-thrombotic occlusion of the mesenteric venules and veins. We present the case of a young man who presented with acute fulminant colitis, requiring colectomy. The differential diagnosis, pathogenesis and treatment are discussed. This case illustrates the rapid progression from ‘well’ to ‘colectomy’ that can occur with MIVOD. MIVOD should be considered in the differential diagnosis of colitis that does not respond to conventional medical treatment

Developing in vitro expanded CD45RA⁺ regulatory T cells as an adoptive cell therapy for Crohn's disease

BACKGROUND AND AIM: Thymus-derived regulatory T cells (T(regs)) mediate dominant peripheral tolerance and treat experimental colitis. T(regs) can be expanded from patient blood and were safely used in recent phase 1 studies in graft versus host disease and type 1 diabetes. T(reg) cell therapy is also conceptually attractive for Crohn's disease (CD). However, barriers exist to this approach. The stability of T(regs) expanded from Crohn's blood is unknown. The potential for adoptively transferred T(regs) to express interleukin-17 and exacerbate Crohn's lesions is of concern. Mucosal T cells are resistant to T(reg)-mediated suppression in active CD. The capacity for expanded T(regs) to home to gut and lymphoid tissue is unknown. METHODS: To define the optimum population for T(reg) cell therapy in CD, CD4(+)CD25(+)CD127(lo)CD45RA(+) and CD4(+)CD25(+)CD127(lo)CD45RA(−) T(reg) subsets were isolated from patients’ blood and expanded in vitro using a workflow that can be readily transferred to a good manufacturing practice background. RESULTS: T(regs) can be expanded from the blood of patients with CD to potential target dose within 22–24 days. Expanded CD45RA(+) T(regs) have an epigenetically stable FOXP3 locus and do not convert to a Th17 phenotype in vitro, in contrast to CD45RA(−) T(regs). CD45RA(+) T(regs) highly express α(4)β(7) integrin, CD62L and CC motif receptor 7 (CCR7). CD45RA(+) T(regs) also home to human small bowel in a C.B-17 severe combined immune deficiency (SCID) xenotransplant model. Importantly, in vitro expansion enhances the suppressive ability of CD45RA(+) T(regs). These cells also suppress activation of lamina propria and mesenteric lymph node lymphocytes isolated from inflamed Crohn's mucosa. CONCLUSIONS: CD4(+)CD25(+)CD127(lo)CD45RA(+) T(regs) may be the most appropriate population from which to expand T(regs) for autologous T(reg) therapy for CD, paving the way for future clinical trials

Spring 1959

Seed testing - A Service for You by Miss Jessie L. Anderson (page 1) Increased Interest in Two-Year Turf Course by Fred P. Jeffrey - Director of Stockbridge (4) From the Editor (4) Message From Winter School President of 1959 (5) Turf club News (6) Number One Graduate (8) Liquid Fertilization by A.B. Longo (9) Public School Grounds by James Woodhouse (12) Comments on the 1959 Winter School (14) Picture - Stockbridge Turf Majors (16) Picture - Honorary Members of Turf Management Club (17) Letter on Chemical Compatibility (18) The Most Outstanding Turf Senior for 1958 (19) What it Means to be a Turf Manager by R. Russell (20) 10 Steps to a Better Lawn by P. Pedrazzi (24) A Scene to Remember (25) I switched from Hots to Cools by J. Spodnik (26) Why Attend Turfgrass Conferences (27) Picture - Winter School for Turf Managers - 1959 (29) Picture - University of Masssachusetts Annual Turfgrass Conference (30) Organic Fertilizers by O.J. Noer (A-1) Inorganic Fertilizers by Charles Winchell (A-1) Urea Formaldehyde by G.F. Stewart (A-2) Phosphorus and Potash Fertilization by Raph Donaldson (A-3) Questions on Fertilization to the Panel (A-4) Cemetery Maintenance by S.E. Robbins (A-6) Lime by Anson Brewer (A-6) Limited Budgets by R.W. Sharkey (A-7) Fertilization of Park Turf by E.J. Pyle (A-7) Disease and Insect Control by Orlando Capizzi (A-8) Cost of Establishing Turf by Victor Taricano (A-9) Question and Answers (A-10) Control of Pests of Ornamentals and Turf Occuring on Golf Courses by John C. Schread (A-12) Behind the Scenes in Soil Testing and What it Means to You Bertram Gersten and Wm. G. Colby (A-19) Lessons Learned from the 1958 Season as Applied to Golf Course Maintenance by A.M. Radko (A-21) The Outlook in Chemical Weed Control on Fine Turf by John Gallagher (A-24) New Developments in Turfgrass Disease Diagnosis and Control by Frank Howard (A-26

Interleukin 6 increases production of cytokines by colonic innate lymphoid cells in mice and patients with chronic intestinal inflammation

Background & Aims: Innate lymphoid cells (ILCs) are a heterogeneous group of mucosal inflammatory cells that participate in chronic intestinal inflammation. We investigated the role of interleukin 6 (IL6) in inducing activation of ILCs in mice and in human beings with chronic intestinal inflammation. Methods: ILCs were isolated from colons of Tbx21-/- × Rag2-/- mice (TRUC), which develop colitis; patients with inflammatory bowel disease (IBD); and patients without colon inflammation (controls). ILCs were characterized by flow cytometry; cytokine production was measured by enzyme-linked immunosorbent assay and cytokine bead arrays. Mice were given intraperitoneal injections of depleting (CD4, CD90), neutralizing (IL6), or control antibodies. Isolated colon tissues were analyzed by histology, explant organ culture, and cell culture. Bacterial DNA was extracted from mouse fecal samples to assess the intestinal microbiota. Results: IL17A- and IL22-producing, natural cytotoxicity receptor-negative, ILC3 were the major subset of ILCs detected in colons of TRUC mice. Combinations of IL23 and IL1α induced production of cytokines by these cells, which increased further after administration of IL6. Antibodies against IL6 reduced colitis in TRUC mice without significantly affecting the structure of their intestinal microbiota. Addition of IL6 increased production of IL17A, IL22, and interferon-γ by human intestinal CD3-negative, IL7-receptor-positive cells, in a dose-dependent manner. Conclusions: IL6 contributes to activation of colonic natural cytotoxicity receptor-negative, CD4-negative, ILC3s in mice with chronic intestinal inflammation (TRUC mice) by increasing IL23- and IL1α-induced production of IL17A and IL22. This pathway might be targeted to treat patients with IBD because IL6, which is highly produced in colonic tissue by some IBD patients, also increased the production of IL17A, IL22, and interferon-γ by cultured human colon CD3-negative, IL7-receptor-positive cells