Expression of Pref-1 and Related Chemokines during the Development of Rat Mesenteric Lymph Nodes

Objective The aim of this study was to investigate the ability of Pref-1~＋ adipocyte progenitor cells to mobilize into mesenteric lymph nodes（MLNs） and the dynamic expression of related chemokines during the development of rat MLNs. Methods Immunohistochemical analyses were used to detect the expression of Pref-1 and related chemokines. Transmission electron microscopy（TEM） was used to observe the changes in ultrastructure of MLNs. Results Cells containing lipid droplets were found in all rat MLNs at embryonic day（E） 18.5, 2 and 6 weeks（w） after birth, and they were similar to fibroblastic reticular cells（FRCs） or follicular dendritic cells（FDCs） under TEM. Pref-1~＋ adipocyte progenitor cells were found in all MLNs. The expression level of Pref-1 was significantly increased at 2 w after birth and decreased at 6 w after birth. The tendency of Cxcl12 expression was consistent with that of Pref-1 and was positively correlated with the expression of Pref-1（P 〈 0.01; r = 0.897）. At E18.5, Cxcl13, and Ccr7 were significantly expressed in the MLN anlage, but the expression level of Ccl21 was low. The expression level of Cxcl13, Ccr7, and Ccl21 in MLN were significantly increased at 2 w after birth（P 〈 0.05）, while the expression of Ccr7 and Ccl21 were significantly decreased at 6 w after birth（P 〈 0.05）. Conclusion Adipocyte progenitor cells are involved in the rat MLNs development through differentiation into FRC and FDC. The expression of the relevant chemokines during the development of MLNs is dynamic and may be related to the maintenance of lymph nodes self-balance state.

Mesenteric lymph node cavitation syndrome

The mesenteric lymph node cavitation syndrome consists of central necrosis of mesenteric lymph nodes and may occur with either celiac disease or a sprue-like intestinal disease that fails to respond to a gluten-free diet. Splenic hypofunction may also be present. The cause is not known but its development during the clinical course of celiac disease is usually indicative of a poor prognosis for the intestinal disorder, a potential for signif icant compli-cations including sepsis and malignancy, particularly T-cell lymphoma, and signif icant mortality. Modern abdominal imaging modalities may permit earlier detection in celiac disease so that earlier diagnosis and improved under-standing of its pathogenesis may result.

Species-or genus-dependent immunostimulatory effects of gut-derived potential probiotics

The immune regulatory effects of probiotics have been widely recognized to be strain-specific.However,it is unknown if there is a species-or genus-dependent manner.In this study,we use an in vitro mesenteric lymph node(MLN)model to systematically evaluate the immunostimulatory effects of gut-derived potential probiotics.The results exhibit an obvious species or genus consensus immune response pattern.RNA-seq shows that T cell-dependent B cell activation and antibody responses may be inherent to this model.Of the five tested genera,Akkermansia spp.and Clostridium butyrium directly activate the immune response in vitro,as indicated by the secretion of interleukin-10.Bifidobacterium spp.and Bacteroides spp.activate immune response with the help of stimuli(anti-CD3 and anti-CD28 antibodies).Lactobacillus spp.blunt the immune response with or without stimuli.Further investigations show that the cell surface protein of A.muciniphila AH39,which may serve as a T cell receptor cognate antigen,might evoke an in vitro immune activation.In vivo,oral administration of A.muciniphila AH39 influences the proportion of T regulatory cells(Tregs)in MLNs and the spleen under homeostasis in both specific pathogen-free and germ-free mice.All these findings indicate the distinct effects of different genera or species of potential gut-derived probiotics on intestinal and systemic immunity.