Inflammatory cytokines produced by activated macrophages largely contribute to the pathological signs of inflammatory bowel disease (IBD). Interleukin-10 (IL-10) is the predominant anti-inflammatory cytokine in the intestine, and its therapeutic efficacy for IBD has been clinically tested. Nevertheless, how the function of IL-10 is regulated in the intestinal microenvironment remains unknown, which largely hinders the further development of IL-10–based therapeutic strategies. Here, we found that the expression of phosphatase Shp2 was increased in colonic macrophages and blood monocytes from IBD patients compared with those from healthy controls. Shp2 deficiency in macrophages protects mice from colitis and colitis-driven colon cancer. Mechanistically, Shp2 disrupts IL-10–STAT3 signaling and its dependent anti-inflammatory response in human and mouse macrophages. Furthermore, a Shp2-inducing role of TNF-α is unveiled in our study. Collectively, our work identifies Shp2 as a detrimental factor for intestinal immune homeostasis and hopefully will be helpful in the future exploitation of IL-10 immunotherapy for IBD.

Overcoming immunosuppression in the tumor microenvironment (TME) is crucial for developing novel cancer immunotherapies. Here, we report that IL-16 administration enhances the polarization of T helper 1 (Th1) cells by inhibiting glutamine catabolism through the downregulation of glutaminase in CD4⁺ T cells and increases the production of Th1 effector cytokine IFN-γ, thus improving anti-tumor immune responses. Moreover, we find that establishing an IL-16-dependent, Th1-dominant TME relies on mast cell-produced histamine and results in the increased expression of the CXCR3 ligands in tumor-associated macrophages (TAM), thereby improving the therapeutic effectiveness of immune checkpoint blockade (ICB). Cancer patients exhibit impaired production of IL-16, which correlates with poorer prognosis. Additionally, low IL-16 production is associated with unresponsiveness to immunotherapy in cancer patients. Collectively, our findings provided new insights into the biological function of IL-16, emphasizing its potential clinical significance as a therapeutic approach to augment anti-tumor immunity and sensitize ICB-based cancer immunotherapy.

Background: Malnutrition is prevalent among patients with inflammatory bowel disease (IBD). Nutritional profiles among Asian patients with IBD have seldom been investigated. We assessed the prevalence of and risk factors for malnutrition, use of nutrition support, and sociopsychological status associated with malnutrition among patients with IBD in China. Methods: Patients with ulcerative colitis and Crohn’s disease (CD) recruited from 43 tertiary referral hospitals were screened for malnutrition and nutrient deficiencies in this cross-sectional study. The use of nutrition support was recorded. The sociopsychological status was assessed by subjective questionnaires. Factors associated with malnutrition were analyzed, and multivariate regression was used to determine independent predictors for malnutrition. Results: We recruited 1013 patients with a median age of 35.0 years, 58.5% of them had CD, and 61.4% of all patients were male. Overall, 49.5% (n = 501) of patients were diagnosed with malnutrition, including 57.0% of patients with CD, 38.8% of patients with ulcerative colitis, and 44.1% of patients with quiescent or mildly active disease. Nutrient deficiencies were prevalent despite the absence of malnutrition. Malnutrition was associated with adverse sociopsychological status, including decreased social support, higher perceived stress, and impaired quality of life. Moderate to severe disease activity and extensive disease were 2 independent risk factors for malnutrition. In total, 41.6% of patients received nutrition support, and patients with risk factors were more likely to receive nutrition support. Conclusions: Malnutrition was highly prevalent and associated with adverse consequences in Chinese patients with IBD. Malnutrition screening and early initiation of nutrition support are essential components in IBD care.

Background: This study aims to explore the epidemiological trends of inflammatory bowel disease (IBD) over the past three decades in China and further predict the trends of IBD in the next 25 years.Methods: The prevalence, incidence, mortality, years of life lived with disability (YLDs), years of life lost (YLLs), disability-adjusted life years (DALYs), and annual percentage changes of the above metrics of IBD in China from 1990 to 2019 were extracted from the Global Burden of Disease Study 2019. The corresponding trends in the next 25 years were predicted.Results: From 1990 to 2019, the cases of IBD in China raised to 484 thousand [95% uncertainty interval (UI) 411–571] and 427 thousand (366–498) among males and females, respectively. The age-standardized incidence rate of IBD increased from 1.72 per 100,000 population (1.44–2.05) to 3.35 per 100,000 population (2.88–3.88) among males and from 1.20 per 100,000 population (1.02–1.42) to 2.65 per 100,000 population (2.29–3.08) among females. The highest incidence rate occurred in people aged 35–39 years. The total YLDs attributed to IBD significantly increased, but the YLLs showed a decreasing trend, resulting in minor alterations of the DALYs. In the next 25 years, the incidence of IBD would continue to increase until a plateau by 2030, and IBD-related deaths would also increase to about 7.57 thousand by 2044 despite the decreasing age-standardized mortality rate. Similar trends were observed for both sexes, with a slight male predominance.Conclusions: Although China is still a low-endemic area of IBD, the prevalence and incidence of IBD dramatically increased in the past three decades. The burden of IBD in China is expected to grow continuously in the next 25 years due to the large population base and severe aging problem. China is estimated to enter the Compounding Prevalence stage around 2030.