scholarly journals CD40-signalling abrogates induction of RORγt+ Treg cells by intestinal CD103+ DCs and causes fatal colitis

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Christian Barthels ◽  
Ana Ogrinc ◽  
Verena Steyer ◽  
Stefanie Meier ◽  
Ferdinand Simon ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Immune Suppression ◽  
Low Frequency ◽  
Treg Cells ◽  
Mesenteric Lymph Nodes ◽  
Mesenteric Lymph ◽  
Cell Induction ◽  
Itreg Cell ◽  
Draining Lymph Nodes ◽  
Dependent Mechanism

Abstract Immune homeostasis in intestinal tissues depends on the generation of regulatory T (Treg) cells. CD103+ dendritic cells (DCs) acquire microbiota-derived material from the gut lumen for transport to draining lymph nodes and generation of receptor-related orphan γt+ (RORγt+) Helios−-induced Treg (iTreg) cells. Here we show CD40-signalling as a microbe-independent signal that can induce migration of CD103+ DCs from the lamina propria (LP) to the mesenteric lymph nodes. Transgenic mice with constitutive CD11c-specific CD40-signalling have reduced numbers of CD103+ DCs in LP and a low frequency of RORγt+Helios− iTreg cells, exacerbated inflammatory Th1/Th17 responses, high titres of microbiota-specific immunoglobulins, dysbiosis and fatal colitis, but no pathology is detected in other tissues. Our data demonstrate a CD40-dependent mechanism capable of abrogating iTreg cell induction by DCs, and suggest that the CD40L/CD40-signalling axis might be able to intervene in the generation of new iTreg cells in order to counter-regulate immune suppression to enhance immunity.

scholarly journals Lactobacillus reuteri DSM 17938 differentially modulates effector memory T cells and Foxp3+ regulatory T cells in a mouse model of necrotizing enterocolitis

2014 ◽  
Vol 307 (2) ◽  
pp. G177-G186 ◽  
Author(s):  
Yuying Liu ◽  
Dat Q. Tran ◽  
Nicole Y. Fatheree ◽  
J. Marc Rhoads
Keyword(s):  
T Cells ◽  
Lymph Nodes ◽  
Necrotizing Enterocolitis ◽  
Lactobacillus Reuteri ◽  
Intestinal Inflammation ◽  
Treg Cells ◽  
T Cell Subsets ◽  
Effector Memory ◽  
Mesenteric Lymph Nodes ◽  
Mesenteric Lymph

Necrotizing enterocolitis (NEC) is an inflammatory disease with evidence of increased production of proinflammatory cytokines in the intestinal mucosa. Lactobacillus reuteri DSM 17938 (LR17938) has been shown to have anti-inflammatory activities in an experimental model of NEC. Activated effector lymphocyte recruitment to sites of inflammation requires the sequential engagement of adhesion molecules such as CD44. The phenotype of CD44+CD45RBlo separates T effector/memory (Tem) cells from naive (CD44−CD45RBhi) cells. It is unknown whether these Tem cells participate in the inflammation associated with NEC and can be altered by LR17938. NEC was induced in 8- to 10-day-old C57BL/6J mice by gavage feeding with formula and exposure to hypoxia and cold stress for 4 days. Survival curves and histological scores were analyzed. Lymphocytes isolated from mesenteric lymph nodes and ileum were labeled for CD4, CD44, CD45RB, intracellular Foxp3, and Helios and subsequently analyzed by flow cytometry. LR17938 decreased mortality and the incidence and severity of NEC. The percentage of Tem cells in the ileum and mesenteric lymph nodes was increased in NEC but decreased by LR17938. Conversely, the percentage of CD4+Foxp3+ regulatory T (Treg) cells in the intestine decreased during NEC and was restored to normal by LR17938. The majority of the Treg cells preserved by LR17938 were Helios+ subsets, possibly of thymic origin. In conclusion, LR17938 may represent a useful treatment to prevent NEC. The mechanism of protection by LR17938 involves modulation of the balance between Tem and Treg cells. These T cell subsets might be potential biomarkers and therapeutic targets during intestinal inflammation.

scholarly journals CCR7-dependent trafficking of RORγ+ ILCs creates a unique microenvironment within mucosal draining lymph nodes

2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Emma C. Mackley ◽  
Stephanie Houston ◽  
Clare L. Marriott ◽  
Emily E. Halford ◽  
Beth Lucas ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Lymphoid Cells ◽  
Intestinal Cells ◽  
Lymphoid Tissues ◽  
Mesenteric Lymph Nodes ◽  
Cell Responses ◽  
Mesenteric Lymph ◽  
Peripheral Lymph ◽  
Group 3 ◽  
Draining Lymph Nodes

Abstract Presentation of peptide:MHCII by RORγ-expressing group 3 innate lymphoid cells (ILC3s), which are enriched within gut tissue, is required for control of CD4 T-cell responses to commensal bacteria. It is not known whether ILC populations migrate from their mucosal and peripheral sites to local draining secondary lymphoid tissues. Here we demonstrate that ILC3s reside within the interfollicular areas of mucosal draining lymph nodes, forming a distinct microenvironment not observed in peripheral lymph nodes. By photoconverting intestinal cells in Kaede mice we reveal constitutive trafficking of ILCs from the intestine to the draining mesenteric lymph nodes, which specifically for the LTi-like ILC3s was CCR7-dependent. Thus, ILC populations traffic to draining lymph nodes using different mechanisms.

scholarly journals Kinetics and distribution of antigen-specific IgE-secreting cells during the primary antibody response in the rat.

1983 ◽  
Vol 157 (6) ◽  
pp. 2178-2183 ◽  
Author(s):  
J D Sedgwick ◽  
P G Holt
Keyword(s):  
Antibody Response ◽  
Lymph Nodes ◽  
Specific Ige ◽  
Assay System ◽  
Organ Distribution ◽  
Primary Immunization ◽  
Mesenteric Lymph Nodes ◽  
Mesenteric Lymph ◽  
Primary Antibody Response ◽  
Draining Lymph Nodes

A new assay system is described for the enumeration of antigen-specific IgE immunoglobulin-secreting cells (ISC) based on an enzyme-linked immunoabsorbent assay. Using this technique to monitor the organ distribution of OVA-specific ISC after primary immunization of rats, approximately 12,000 specific IgE ISC were detected at the peak of the response in the draining lymph nodes compared with 117,000 IgG ISC; the splenic anti-OVA response was restricted to the IgM class. Using plates precoated with anti-rat IgE instead of antigen, total IgE ISC were enumerated in normal and helminth-parasitized rats. The assay system detected up to 5 X 10(5) IgE ISC in mesenteric lymph nodes from parasitized animals compared with less than 50 in controls.

Early lymphocytic responses to Heligmosomoides polygyrus infections in mice

1990 ◽  
Vol 64 (1) ◽  
pp. 35-45 ◽  
Author(s):  
S. J. Parker ◽  
C. J. Inchley
Keyword(s):  
Lymph Nodes ◽  
Lymphoid Tissues ◽  
Mesenteric Lymph Nodes ◽  
Heligmosomoides Polygyrus ◽  
Intestinal Nematode ◽  
Mesenteric Lymph ◽  
Low Responder ◽  
Proliferating Cell ◽  
Draining Lymph Nodes

ABSTRACTResponses to parasite antigens were studied in three strains of mice, BALB/c, CBA and NIH, during the initial phases of a primary infection with the intestinal nematode Heligmosomoides polygyrus. Changes in the rate of in vivo cell division were analysed in mesenteric lymph nodes and spleens during the phases of larval maturation and adult establishment, and related to changes in organ size and cellularity. The nature of the proliferating cell populations was also investigated by flow cytometry, carried out on cell suspensions prepared at the time when larval development was complete. The variation in the ability of the strains of mice to become resistant to a challenge infection was manifest as only slight differences in their initial responses to infection. All three strains showed an increase in 125I-iododeoxyuridine incorporation in their mesenteric lymph nodes and spleen, and an increase in B cell frequency over that of T cells in the draining lymph nodes. Although lymph node weight in NIH mice continued to rise over a 4 week period, the majority of responses measured were short lived, peaking 10 to 14 days after infection. The low responder status of CBA mice was thus reflected in a transient and relatively small enlargement of lymphoid tissues, but their early proliferative responses to antigen were similar in scale to those of responder strains.

In situ demonstration of migration of dendritic cells released from rat small intestine to mesenteric lymph nodes

2001 ◽  
Vol 120 (5) ◽  
pp. A183-A183
Author(s):  
H KOBAYASHI ◽  
H NAGATA ◽  
S MIURA ◽  
T AZUMA ◽  
H SUZUKI ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Small Intestine ◽  
Lymph Nodes ◽  
Rat Small Intestine ◽  
Mesenteric Lymph Nodes ◽  
Mesenteric Lymph

scholarly journals The microbiota is dispensable for the early stages of peripheral regulatory T cell induction within mesenteric lymph nodes

2021 ◽  
Author(s):  
Carolin Wiechers ◽  
Mangge Zou ◽  
Eric Galvez ◽  
Michael Beckstette ◽  
Maria Ebel ◽  
...  
Keyword(s):  
T Cell ◽  
Lymph Nodes ◽  
Regulatory T Cell ◽  
De Novo ◽  
Bacterial Species ◽  
Short Chain Fatty Acids ◽  
Mesenteric Lymph Nodes ◽  
Direct Role ◽  
Early Stages ◽  
Mesenteric Lymph

AbstractIntestinal Foxp3+ regulatory T cell (Treg) subsets are crucial players in tolerance to microbiota-derived and food-borne antigens, and compelling evidence suggests that the intestinal microbiota modulates their generation, functional specialization, and maintenance. Selected bacterial species and microbiota-derived metabolites, such as short-chain fatty acids (SCFAs), have been reported to promote Treg homeostasis in the intestinal lamina propria. Furthermore, gut-draining mesenteric lymph nodes (mLNs) are particularly efficient sites for the generation of peripherally induced Tregs (pTregs). Despite this knowledge, the direct role of the microbiota and their metabolites in the early stages of pTreg induction within mLNs is not fully elucidated. Here, using an adoptive transfer-based pTreg induction system, we demonstrate that neither transfer of a dysbiotic microbiota nor dietary SCFA supplementation modulated the pTreg induction capacity of mLNs. Even mice housed under germ-free (GF) conditions displayed equivalent pTreg induction within mLNs. Further molecular characterization of these de novo induced pTregs from mLNs by dissection of their transcriptomes and accessible chromatin regions revealed that the microbiota indeed has a limited impact and does not contribute to the initialization of the Treg-specific epigenetic landscape. Overall, our data suggest that the microbiota is dispensable for the early stages of pTreg induction within mLNs.

Pericolic mesenteric lymph nodes: an aid in distinguishing diverticulitis from cancer of the colon.

1997 ◽  
Vol 169 (5) ◽  
pp. 1253-1255 ◽  
Author(s):  
K N Chintapalli ◽  
C C Esola ◽  
S Chopra ◽  
A A Ghiatas ◽  
G D Dodd
Keyword(s):  
Lymph Nodes ◽  
Mesenteric Lymph Nodes ◽  
Mesenteric Lymph
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