Ontogeny of RORγt+ cells in the intestine of newborns and its role in the development of experimental necrotizing enterocolitis

Background Neonates possess an immature and plastic immune system, which is a major cause of some diseases in newborns. Necrotizing enterocolitis (NEC) is a severe and devastating intestinal disease that typically affects premature infants. However, the development of intestinal immune cells in neonates and their roles in the pathological process of NEC have not been elucidated. Results We examined the ontogeny of intestinal lamina propria lymphocytes in the early life of mice and found a high percentage of RORγt+ cells (containing inflammatory Th17 and ILC3 populations) during the first week of life. Importantly, the proportion of RORγt+ cells of intestinal lamina propria further increased in both NEC mice and patients tissue than the control. Furthermore, the application of GSK805, a specific antagonist of RORγt, inhibited IL-17A release and ameliorated NEC severity. Conclusions Our data reveal the high proportion of RORγt+ cells in newborn mice may directly contribute to the development of NEC.

Antiretroviral Therapy Dampens Mucosal CD4+ T Lamina Propria Lymphocytes Immune Activation in Long-Term Treated People Living with HIV-1

HIV infection is characterized by a severe deterioration of an immune cell-mediated response due to a progressive loss of CD4+ T cells from gastrointestinal tract, with a preferential loss of IL-17 producing Th cells (Th17), a specific CD4+ T cells subset specialized in maintaining mucosal integrity and antimicrobial inflammatory responses. To address the effectiveness of antiretroviral therapy (ART) in reducing chronic immunological dysfunction and immune activation of intestinal mucosa, we conducted a cross-sectional observational study comparing total IFN-γ-expressing (Th1) and IL-17-expressing (Th17) frequencies of CD4+ T lamina propria lymphocytes (LPLs) and their immune activation status between 11 male ART-naïve and 11 male long-term ART-treated people living with HIV-1 (PLWH) who underwent colonoscopy and retrograde ileoscopy for biopsies collection. Flow cytometry for surface and intracellular staining was performed. Long-term ART-treated PLWH showed lower levels of CD38+ and/or HLA-DR+ LPLs compared to ART-naïve PLWH. Frequencies of Th1 and Th17 LPLs did not differ between the two groups. Despite ART failing to restore the Th1 and Th17 levels within the gut mucosa, it is effective in increasing overall CD4+ T LPLs frequencies and reducing mucosal immune activation.

Effect of Inorganic Zinc on Selected Immune Parameters in Chicken Blood and Jejunum after A. galli Infection

Ascaridiosis in poultry results in a reduction in body weight gain, egg production, as well as microelement levels. Infected poultry have higher demands on feed with the addition of essential elements including zinc. The effects of the infection by Ascaridia galli and the supplementation of inorganic zinc on the immune status of broilers were monitored through evaluation of the relative expression of selected genes (interleukins, IFN-γ, and TNF-α) by real-time PCR, haematology parameters by microscopy, and quantitative changes of lamina propria lymphocytes by flow cytometry in day 7 and day 14 of the study. We observed that the enrichment of the diet with inorganic zinc has a positive effect on the relative percentage of CD4+ lamina propria lymphocytes in the jejunum and on heterophil counts in blood. In addition, it was concluded that inorganic zinc has an anti-inflammatory effect (downregulation of TNF-α and IL-17) and activates IgA-producing cells in the jejunum of chicks infected with A. galli.

Innate lymphoid cells facilitate NK cell development through a lymphotoxin-mediated stromal microenvironment

Natural killer (NK) cell development relies on signals provided from the bone marrow (BM) microenvironment. It is thought that lymphotoxin (LT) α1β2 expressed by the NK cell lineage interacts with BM stromal cells to promote NK cell development. However, we now report that a small number of RORγt+ innate lymphoid cells (ILCs), and not CD3−NK1.1+ cells, express LT to drive NK development. Similar to LT−/− or RORγt−/− mice, the mice conditionally lacking LTα1β2 on RORγt+ ILCs experience a developmental arrest at the immature NK stages, between stages of NK development to the mature NK cell stage. This developmental block results in a functional deficiency in the clearance of NK-sensitive tumor cells. Reconstitution of Thy1+ ILCs from BM or purified RORγt+ ILCs from lamina propria lymphocytes into LT-deficient RORγt+ BM cultures rescues NK cell development. These data highlight a previously undiscovered role of RORγt+ ILCs for NK cell development and define LT from ILCs as an essential molecule for the stromal microenvironment supporting NK cell development.