The ectoenzymes CD39 and CD73 play a major role in controlling tissue inflammation by regulating the balance between adenosine triphosphate (ATP) and adenosine. Still, little is known about the role of these two enzymes and ATP and its metabolites in the pathophysiology of inflammatory bowel disease (IBD). We isolated mononuclear cells from peripheral blood and lamina propria of the large intestine of patients diagnosed with IBD and of healthy volunteers. We then comprehensively analyzed the CD39 and CD73 expression patterns together with markers of activation (HLA-DR, CD38), differentiation (CCR7, CD45RA) and tissue-residency (CD69, CD103, CD49a) on CD4 + , CD8 + , γδ + T cells and mucosa-associated invariant T cells using flow cytometry. CD39 expression levels of γδ + and CD8 + T cells in lamina propria lymphocytes (LPL) were much higher compared to peripheral blood mononuclear cells. Moreover, the frequency of CD39 + CD4 + and CD8 + , but not γδ + LPL positively correlated with T-cell activation. The frequency of CD39 + cells among tissue-resident memory LPL (Trm) was higher compared to non-Trm for all subsets, confirming that CD39 is a marker for the tissueresident memory phenotype. γδ + Trm also showed a distinct cytokine profile upon stimulation-the frequency of IFN-γ + and IL-17A + cells was significantly lower in γδ + Trm compared to non-Trm. Interestingly, we observed a decreased frequency of CD39 + γδ + T cells in IBD patients compared to healthy controls (p = 0.0049). Prospective studies need to elucidate the exact role of this novel CD39 + γδ + T-cell population with tissue-resident memory phenotype and its possible contribution to the pathogenesis of IBD and other inflammatory disorders.

Introduction: Carcinoid syndrome is the most frequent functional syndrome of neuroendocrine neoplasia. It is characterized by flushing, diarrhea, wheezing, hypotension, and exanthema and may cause carcinoid heart disease. Methods: We assessed clinical characteristics and prognosis of patients with carcinoid syndrome and carcinoid heart disease in 276 patients from 3 referral centers. Results: Carcinoid syndrome patients had a mean age of 57 years (range 21–84) and a normal BMI of 24.9 (SD 4.5; range 13.8–39.6). Most primaries were of small bowel or unknown primaries with distant metastasis in 94.6%. Flushing was the most frequent symptom in 74.3% of patients, followed by diarrhea in 68.8%, and wheezing in 40.9%. Pain was described by 45.3%, weakness by 23.5%, and weight loss of >10% in 6 months by 30.1% of patients. Carcinoid heart disease was diagnosed in 37.3% of patients (n = 104) by echocardiography and involved predominantly in the tricuspid valve. Combinations with other valve defects were common. Somatostatin analogs were taken by 80.4% of patients and 17% needed additional loperamide/opium tincture. Surgery and peptide receptor radiotherapy were most frequent treatments. The median survival of patients with carcinoid syndrome after diagnosis was 9 years. Prognosis was significantly impaired by male sex and diagnosis of carcinoid heart disease but surprisingly significantly increased by the presence of symptoms flushing and weakness. Discussion/Conclusion: Carcinoid syndrome is associated with extensive disease and primaries in small bowels or of unknown primary. Weight loss, weakness, and pain are frequent, and carcinoid heart disease is diagnosed in more than one-third of patients.