Organizing a mucosal defense

Newberry, Rodney D.; Lorenz, Robin G.

doi:10.1111/j.0105-2896.2005.00282.x

Cited by 126 publications

(94 citation statements)

References 137 publications

(246 reference statements)

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“…The endogenous Hec-6st gene is known to be expressed in sites other than HEV (6, 7), and there was an unexpected LacZ expression in intestinal villi, which did not correlate with PNAd (data not shown). The villi are sites of lymphocyte recruitment and differentiation into isolated lymphoid follicles (23,24). Further studies are needed to investigate whether this expression is authentic but had not previously been noted as a trafficking mechanism.…”

Section: Resultsmentioning

confidence: 99%

Transgenic LacZ under control of Hec-6st regulatory sequences recapitulates endogenous gene expression on high endothelial venules

Liao

Bentley

Lebrun

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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Hec-6st is a highly specific high endothelial venule (HEV) gene that is crucial for regulating lymphocyte homing to lymph nodes (LN). The enzyme is also expressed in HEV-like vessels in tertiary lymphoid organs that form in chronic inflammation in autoimmunity, graft rejection, and microbial infection. Understanding the molecular nature of Hec-6st regulation is crucial for elucidating its function in development and disease. However, studies of HEV are limited because of the difficulties in isolating and maintaining the unique characteristics of these vessels in vitro. The novel pClasper yeast homologous recombination technique was used to isolate from a BAC clone a 60-kb DNA fragment that included the Hec-6st (Chst4) gene with flanking sequences. Transgenic mice were generated with the ␤-galactosidase (LacZ) reporter gene inserted in-frame in the exon II of Hec-6st within the isolated BAC DNA fragment. LacZ was expressed specifically on HEV in LN, as indicated by its colocalization with peripheral node vascular addressin. LacZ was increased in nasal-associated lymphoid tissue during development and was reduced in LN and nasal-associated lymphoid tissue by LT␤R-Ig (lymphotoxin-␤ receptor human Ig fusion protein) treatment in a manner identical to the endogenous gene.The transgene was expressed at high levels in lymphoid accumulations with characteristics of tertiary lymphoid organs in the salivary glands of aged mice. Thus, the Hec-6st-LacZ construct faithfully reproduces Hec-6st tissue-specific expression and can be used in further studies to drive expression of reporter or effector genes, which could visualize or inhibit HEV in autoimmunity.lymphoid organ ͉ pClasper ͉ peripheral node vascular addressin ͉ sulfotransferase ͉ lymphotoxin H igh endothelial venules (HEV) are the site of entry of naïve lymphocytes into the lymph node (LN) parenchyma from the blood stream. Lymphocyte tethering along HEV in LN is mediated by the interaction of L-selectin expressed on the surface of lymphocytes and L-selectin ligands expressed on HEV.

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Section: Resultsmentioning

confidence: 99%

Transgenic LacZ under control of Hec-6st regulatory sequences recapitulates endogenous gene expression on high endothelial venules

Liao

Bentley

Lebrun

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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“…Although ILF have long been known to be present in the intestines of numerous species, these structures had been generally neglected in most studies addressing PP function, thereby disregarding their potential in supporting intestinal immune responses (8,33). Different models have been put forward that describe key features of ILF formation (11). In utero treatment of pregnant mice with lymphotoxin-␤ receptor fusion proteins, which is the most frequently used method to prevent PP formation, augments the frequency of large-sized ILF.…”

Section: Discussionmentioning

confidence: 99%

Adaptation of Solitary Intestinal Lymphoid Tissue in Response to Microbiota and Chemokine Receptor CCR7 Signaling

Pabst

Herbrand

Friedrichsen

et al. 2006

The Journal of Immunology

144

136

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Besides Peyer’s patches, solitary intestinal lymphoid tissue (SILT) provides a structural platform to efficiently initiate immune responses in the murine small intestine. SILT consists of dynamic lymphoid aggregates that are heterogeneous in size and composition, ranging from small clusters of mostly lineage-negative cells known as cryptopatches to larger isolated lymphoid follicles rich in B cells. In this study, we report that in chemokine receptor CCR7-deficient mice SILT is enlarged, although unchanged in frequency and cellular composition compared with wild-type mice. This phenotype is conferred by bone marrow-derived cells and is independent of the presence of intestinal bacteria. Remarkably, particularly small-sized SILT predominates in germfree wild-type mice. Colonization of wild-type mice with commensal bacteria provokes an adjustment of the spectrum of SILT to that observed under specific pathogen-free conditions by the conversion of pre-existing lymphoid structures into larger-sized SILT. In conclusion, our findings establish that intestinal microbes influence the manifestation of gut-associated lymphoid tissues and identify CCR7 signaling as an endogeneous factor that controls this process.

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“…Isolated lymphoid follicles (ILFs), also referred to as solitary lymphoid follicles (4,5), are part of this mucosal immune machinery (6)(7)(8)(9) and can be clearly distinguished from Peyer's patches (PPs) (10,11). Mature ILFs contain a germinal center (GC) with mainly follicular B-lymphocytes (12), CD4 þ follicular helper T cells (T FH ) (13) and follicular dendritic cells (14).…”

Section: Introductionmentioning

confidence: 99%

Immunological Status of Isolated Lymphoid Follicles After Intestinal Transplantation

Meier

Docena

Ramisch

et al. 2014

American Journal of Transplantation

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Intestinal transplantation (ITx) faces the challenge of grafting a high immunogenic organ, which is certainly one of the major obstacles for intestinal allograft acceptance. The allograft has to guarantee the proper functioning of the mucosal immune machinery under immunosuppressive conditions. Recently, it has been elucidated that isolated lymphoid follicles (ILFs) are an indispensable part of mucosal immunity to maintain IgA synthesis and consequently to control commensal microflora. No data about these follicular structures in the setting of ITx are available so far. Therefore, we addressed the question whether constitution, integrity and function of allograft ILFs are disturbed by immunosuppressive regimen. We compared allograft ILFs from terminal ileum of transplant patients with ILFs from nontransplant patients via flow cytometry, quantitative real-time polymerase chain reaction and immunohistochemistry. We found that host leukocytes rapidly repopulate allograft ILFs and that maintenance immunosuppressive regimen, tacrolimus and corticosteroids, does not affect their cellular integrity and function. However, allograft ILFs revealed a higher maturation state than control samples and IgA positive plasma cells were increased in number in allograft mucosa. Our results open the path for a better understanding of allograft mucosal immunity.

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Organizing a mucosal defense

Cited by 126 publications

References 137 publications

Transgenic LacZ under control of Hec-6st regulatory sequences recapitulates endogenous gene expression on high endothelial venules

Transgenic LacZ under control of Hec-6st regulatory sequences recapitulates endogenous gene expression on high endothelial venules

Adaptation of Solitary Intestinal Lymphoid Tissue in Response to Microbiota and Chemokine Receptor CCR7 Signaling

Immunological Status of Isolated Lymphoid Follicles After Intestinal Transplantation

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