Pulmonary lymphoproliferative disorders in children: a practical review.

Pulmonary lymphoproliferative disorders represent an uncommon spectrum of proliferation of lymphoid tissue in the lung parenchyma ranging from benign hyperplasia to malignancy. They tend to occur in certain clinical situations and have typical imaging features that together can be used by the radiologist to suggest these entities as part of the differential diagnosis. We review key clinical, histopathological and computed tomography features of pulmonary lymphoproliferative disorders in children including follicular bronchiolitis, lymphoid interstitial pneumonia, granulomatous-lymphocytic interstitial lung disease, lymphoma and post-transplant lymphoproliferative disorder to familiarize the pediatric radiologist with this group of disorders.

Lemmel Syndrome Secondary to Duodenal Diverticulitis: A Case Report.

Lemmel syndrome occurs when a duodenal diverticulum causes obstructive jaundice due to a mechanical obstruction of the common bile duct. Additional pathophysiologic processes may also contribute to the development of Lemmel syndrome. These include duodenal diverticula causing dysfunction of the sphincter of Oddi as well as compression of the common bile duct by duodenal diverticula. It is uncommon for duodenal diverticulum to become inflamed. We report the case of a 25-year-old female presenting with unintentional weight loss and fatigue. Since her initial labs were concerning for possible infection with hepatobiliary abnormalities, a contrast-enhanced CT was obtained. This study revealed a large periampullary diverticulum with mucosal enhancement and fat stranding consistent with diverticulitis.

The chemokine receptor CCR9 is required for the T-cell-mediated regulation of chronic ileitis in mice.

BACKGROUND & AIMS: A balance between effector and regulatory T-cell (Treg) responses is required to maintain intestinal homeostasis. To regulate immunity, T cells migrate to the intestine using a combination of adhesion molecules and chemokine receptors. However, it is not known whether the migration pathways of effector cells and Tregs are distinct or shared. We sought to determine whether interaction between the chemokine receptor 9 (CCR9) and its ligand, chemokine ligand 25 (CCL25), allows effectors or Tregs to localize to chronically inflamed small intestine. METHODS: By using a mouse model that develops Crohn's-like ileitis (tumor necrosis factor Δadenosine uracyl-rich element [TNFΔARE] mice) we examined the role of CCL25-CCR9 interactions for effector and Treg traffic using flow cytometry, quantitative reverse-transcription polymerase chain reaction, immunohistochemistry, immunoneutralization, and proliferation analyses. RESULTS: In TNFΔARE mice, expression of CCL25 and the frequency of CCR9-expressing lymphocytes increased during late-stage disease. In the absence of CCR9, TNFΔARE mice developed exacerbated disease, compared with their CCR9-sufficient counterparts, which coincided with a deficiency of CD4(+)/CD25(+)/forkhead box P3(+) and CD8(+)/CD103(+) Tregs within the intestinal lamina propria and mesenteric lymph nodes. Furthermore, the CD8(+)/CCR9(+) subset decreased the proliferation of CD4(+) T cells in vitro. Administration of a monoclonal antibody against CCR9 to TNFΔARE mice exacerbated ileitis in vivo, confirming the regulatory role of CD8(+)/CCR9(+) cells. CONCLUSIONS: Signaling of the chemokine CCL25 through its receptor CCR9 induces Tregs to migrate to the intestine. These findings raise concerns about the development of reagents to disrupt this pathway for the treatment of patients with Crohn's disease.

Novel model of TH2-polarized chronic ileitis: the SAMP1 mouse.

BACKGROUND: SAMP1/Yit mice develop spontaneous, segmental, transmural ileitis recapitulating many features of Crohn's disease (CD). The ileitic phenotype may have arisen during crosses of SAMP1 mice selected for the presence of skin lesions. We hereby describe that the original SAMP1 strain similarly develops ileitis. Our aim was to characterize the histopathological and immunological features of this model and assess its responsiveness to standard inflammatory bowel disease (IBD) therapy. METHODS: The time course of histopathological features of ileitis was assessed. Immune compartments were characterized by flow cytometry. Ileal cytokine profiles and transcription factors were determined by real-time reverse-transcription polymerase chain reaction (RT-PCR). Finally, response to corticosteroid therapy and its effect on immune compartments and cellularity was evaluated. RESULTS: Histological features and time course of disease were conserved, compared to those reported in SAMP1/Yit strains, with similar expansion of CD19+, CD4+, and CD8+ effector (CD44(high) CD62L(low)), and central memory lymphocytes (CD44(high)CD62L(high)). However, different from SAMP1/YitFc mice, analysis of ileal cytokine profiles revealed initial T(H)1 polarization followed by T(H)2-polarized profile accompanied by prominent eosinophilia during late disease. Lastly, corticosteroids attenuated ileitis, resulting in decreased lymphocyte subsets and cellularity of compartments. CONCLUSIONS: Here we report that the ileitic phenotype of SAMP1-related strains was already present in the original SAMP1 strain. By contrast, the cytokine profile within the terminal ilea of SAMP1 is distinct from the mixed T(H)1/T(H)2 profile of SAMP1/YitFc mice during late disease, as it shows predominant T(H)2 polarization. Dissemination of these strains may advance our understanding of CD pathogenesis, which in 60% of patients involves the terminal ileum.

CD44 deficiency attenuates chronic murine ileitis.

BACKGROUND & AIMS: Lymphocyte recruitment to sites of inflammation requires the sequential engagement of adhesion molecules and chemokine receptors. In the current studies we analyzed the role of CD44 for the development of chronic small-intestinal inflammatory infiltrates in vivo. METHODS: By using a tumor necrosis factor (TNF)-driven model of chronic ileitis (ie, B6.129P-TNF(DeltaAU-rich element [ARE])) that recapitulates many features of Crohn's disease, we noticed dynamic changes in the expression and functional state of CD44 and its ligand hyaluronan via enzyme-linked immunosorbent assay, real-time reverse-transcription polymerase chain reaction, immunohistochemistry, and flow cytometry. In addition, we assessed the role of lymphocyte populations during induction of ileitis through adoptive transfer studies, and generated CD44-deficient TNFDeltaARE mice to assess the role of CD44 for development of ileitis. RESULTS: Soluble hyaluronan levels and expression of hyaluronan synthase-1 were increased in TNFDeltaARE mice. This coincided with increased expression of CD44 (including variant 7) and reactivity towards hyaluronan on CD4(+) T cells. CD44 was spatially colocalized with the gut-homing integrin alpha(4)beta(7), spatially linking lymphocyte rolling with arrest. These cells had an effector phenotype because they lacked L-selectin and a higher proportion in diseased mice produced TNF and interleukin-2 compared with wild-type littermates. Lastly, CD4(+) but not CD8(+) T cells conferred ileitis to RAG(-/-) recipients and deficiency of one or both alleles of the CD44 gene resulted in attenuation of the severity of ileitis in TNFDeltaARE mice. CONCLUSIONS: Our findings support an important role of CD44 expressed by CD4(+) and CD8(+) for development of ileitis mediated by TNF overproduction.