Network of dendritic cells within the muscular layer of the mouse intestine

Flores‐Langarica, Adriana; Meza-Pérez, Selene; Calderón‐Amador, Juana; Estrada-García, Teresa; MacPherson, G. Gordon; Lebecque, Serge; Saeland, Sem; Steinman, Ralph M.; Flores‐Romo, Leopoldo

doi:10.1073/pnas.0504253102

Cited by 58 publications

(46 citation statements)

References 35 publications

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“…For example, Tregs are often located at the interface of antigen-presenting cells (APCs) and Teffs supporting a role of APC-Treg interaction for Treg activation and/or migration and function (13). Interestingly, we found an increase in CD45 + CD3 -CD11b + MHC hi APCs, which we further identified as CD11c + DEC-205 + lamina propria DCs (37) in the wTregs-transferred HO-1 + Het pups (Supplementary Figure S3c online). This increase in APCs indicates that Tregs injected intraperitoneally can indeed migrate to the intestine.…”

Section: Correlation Of Treg/teff Ratios and Nec Scoresmentioning

confidence: 65%

Heme oxygenase-1 confers protection and alters T-cell populations in a mouse model of neonatal intestinal inflammation

et al. 2015

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Background: Necrotizing enterocolitis (NEC), an intestinal inflammatory disease affecting premature infants, is associated with low regulatory T (Treg) to effector T (Teff ) cell ratios. We recently demonstrated that heme oxygenase-1 (HO-1) deficiency leads to increased NEC development. Here, we investigated the effects of HO-1 on T-cell proportions in a murine NEC-like injury model. Methods: Intestinal injury was induced in 7-d-old wildtype (WT) or HO-1 heterozygous (HO-1 Het) pups by formulafeeding every 4 h for 24-78 h by oral gavage and exposures to 5%O 2 . Controls remained breastfed. HO-1 was induced in WT pups by administering heme preinjury induction. Lamina propria T cells were identified by flow cytometry. For adoptive transfer studies, WT splenic/thymic Tregs were injected intraperitoneally into HO-1 Het pups 12-24 h preinduction. results: Het mice showed increased intestinal injury and decreased Treg/Teff ratios. Genes for pattern recognition (Toll-like receptor-4, C-reactive protein, MyD88) and neutrophil recruitment increased in Het pups after NEC induction. Inducing intestinal HO-1 decreased NEC scores and incidence, and increased Treg/Teff ratios. Moreover, adoptive transfer of Tregs from WT to HO-1 Het pups decreased NEC scores and incidence and restored Treg/Teff ratios. conclusion: HO-1 can change Treg proportions in the lamina propria of young mice under inflammatory conditions, which might, in part, confer intestinal protection.n EC is a devastating disease of premature infants.Characterized by intestinal inflammation, it can progress rapidly to intestinal necrosis. Its incidence correlates inversely with low birth weight and gestational age, reaching ~7% in infants weighing 500-1,500 g. Unfortunately, 20-40% of NEC patients need to undergo surgery, which increases mortality up to 50% and places these infants at higher risk for developing long-term sequelae, such as short bowel syndrome and neurodevelopmental impairments (1).Although advances in the understanding of its pathophysiology have been made in the last decades, the pathogenesis of NEC remains incompletely understood. Thus, current prevention and treatment strategies are limited. Three factors are generally present when NEC occurs: (i) an immature intestinal barrier and immune system; (ii) enteral feedings; and (iii) a putative bacterial component. A genetic predisposition, an in utero maternal or fetal insult (hypoxia), and/or a highly immune-reactive intestinal mucosa may then cause the initial inflammation that precedes NEC (2).Several studies have demonstrated the importance of the innate immune system in the pathophysiology of NEC. For example, a significant component is the pattern recognition of pathogens through Toll-like receptor (TLR)-4 (3,4). Also, a reduction in Paneth and in mucin-producing goblet cells (5,6) and an increase in proinflammatory mediators (i.e., TNF-α, IL-1, -6, -8, and platelet-activating factor) are associated with NEC (7).However, less attention has been given to the adaptive immune system. The fact th...

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Section: Correlation Of Treg/teff Ratios and Nec Scoresmentioning

confidence: 65%

Heme oxygenase-1 confers protection and alters T-cell populations in a mouse model of neonatal intestinal inflammation

et al. 2015

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“…These mice have not only greatly improved our understanding of the behavior of endogenous DCs in the LN (Lindquist et al 2004;Shakhar et al 2005), but also their roles in various models of infection (Aoshi et al 2008;Hapfelmeier et al 2008;Veres et al 2007). They also enabled the visualization of intestinal DCs (Flores-Langarica et al 2005) and the identiWcation of a previously uncharacterized population of DCs in the brain (Bulloch et al 2008). In the skin of these mice, both LCs and DDCs express the transgene (although expression is generally higher in DDCs compared to LCs), and can therefore be identiWed with minimal sample preparation (Ng et al 2008).…”

Section: Lcs and Ddcs In The Skin In Vivo: Lessons From Confocal Micrmentioning

confidence: 99%

Visualizing dendritic cell migration within the skin

Roediger

Smith

et al. 2008

Histochem Cell Biol

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Dendritic cells (DCs) within the skin are a heterogeneous population of cells, including Langerhans cells of the epidermis and at least three subsets of dermal DCs. Collectively, these DCs play important roles in the initiation of adaptive immune responses following antigen challenge of the skin as well as being mediators of tolerance to self-antigen. A key functional aspect of cutaneous DCs is their migration both within the skin and into lymphatic vessels, resulting in their emigration to draining lymph nodes. Here, we discuss our current understanding of the requirements for successful DC migration in and from the skin, and introduce some of the microscopic techniques developed in our laboratory to facilitate a better understanding of this process. In particular, we detail our current use of multi-photon excitation (MPE) microscopy of murine skin to dissect the migratory behavior of DCs in vivo.

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“…This suggests that the IM-associated accumulation of dendritic cells is due not to an immigration of activated CCR7 ϩ/ϩ dendritic cells but to an on-site activation of resident or immigrating immature dendritic cells. Additionally, CCR7 is involved in the enhancement (5,6,15,34,56,65) and perpetuation (15,17,18,24,30,46,58,60,64,74) of jejunal inflammation after standardized jejunal manipulation. CCR7 is expressed on mature, activated dendritic cells.…”

Section: Discussionmentioning

confidence: 99%

Impact of CCR7 on the gastrointestinal field effect

Koscielny

Engel

Maurer

et al. 2011

American Journal of Physiology-Gastrointestinal and Liver Physi

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.2010.-Standardized intestinal manipulation (IM) leads to local bowel wall inflammation subsequently spreading over the entire gastrointestinal tract. Previously, we demonstrated that this so-called gastrointestinal field effect (FE) is immune mediated. This study aimed to investigate the role of CCR7 in IM-induced FE. Since CCR7 is expressed on activated dendritic cells and T cells and is well known to control their migration, we hypothesized that lack of CCR7 reduces or abolishes FE. Small bowel muscularis and colonic muscularis from CCR7Ϫ/Ϫ and wild-type (WT) mice were obtained after IM of the jejunum or sham operation. FE was analyzed by measuring gastrointestinal transit time of orally given fluorescent dextran (geometric center), colonic transit time, infiltration of MPO-positive cells, and circular smooth muscle contractility. Furthermore, mRNA levels of the inflammatory cytokine IL-6 were determined by RT-PCR. The number of dendritic cells and CD3ϩCD25ϩ T cells separately isolated from jejunum and colon was determined in mice after IM and sham operation. There was no significant difference in IL-6 mRNA upregulation in colonic muscularis between sham-operated WT and CCR7 Ϫ/Ϫ mice after IM. Contractility of circular muscularis strips of the colon was significantly improved in CCR7 Ϫ/Ϫ animals following IM and did not vary significantly from sham-operated animals. Additionally, inflammation of the colon determined by the number of MPO-positive cells and colonic transit time was significantly reduced in CCR7 Ϫ/Ϫ mice. In contrast, jejunal contractility and jejunal inflammation of transgenic mice did not differ significantly from WT mice after IM. These data are supported by a significant increase of CD3ϩCD25ϩ T cells in the colonic muscularis of WT mice after IM, which could not be observed in CCR7Ϫ/Ϫ mice. These data demonstrate that CCR7 is required for FE and postoperative ileus. CCR7 indirectly affects FE by inhibiting migration of activated dendritic cells and of T cells from the jejunum to the colon. These findings support the critical role of the adaptive immune system in FE. postoperative ileus; chemokine receptor 7 POSTOPERATIVE ILEUS (POI) is an inevitable sequela of abdominal surgery or trauma with a variably gradual manifestation. It leads to postoperative discomfort, prolonged hospitalization, and increased patient morbidity and has a high impact on socioeconomic costs (27,43,49,63). The pathophysiology of POI and postoperative gastrointestinal dysmotility, respectively, has been elucidated in recent years. POI is marked by a neurogenic phase and a clinically relevant prolonged inflammatory phase. Both the neuronal activation by intestinal manipulation (IM) and inflammatory cell infiltrates in the intestinal muscularis compromise gastrointestinal motility. These detrimental alterations are emphasized as major factors in the development of POI (4,8,9,15,16,[35][36][37][38][40][41][42]. We reported a time-and trauma-degree-dependent inflammatory cascade (35, 36); infiltration of leukocytes (40 -42...

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Network of dendritic cells within the muscular layer of the mouse intestine

Cited by 58 publications

References 35 publications

Heme oxygenase-1 confers protection and alters T-cell populations in a mouse model of neonatal intestinal inflammation

Heme oxygenase-1 confers protection and alters T-cell populations in a mouse model of neonatal intestinal inflammation

Visualizing dendritic cell migration within the skin

Impact of CCR7 on the gastrointestinal field effect

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