Plasmablast frequency and trafficking receptor expression are altered in pediatric ulcerative colitis

Tarlton, Nicole J.; Green, Caroline M.; Lazarus, Nicole H.; Rott, Lusijah S.; Wong, Anthony; Abramson, Oren; Bremer, Martina; Butcher, Eugene C.; Abramson, Tzvia

doi:10.1002/ibd.22962

Cited by 19 publications

(19 citation statements)

References 37 publications

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“…Using flow cytometry, Kantele et al observed α4β7 expression by ASCs after oral vaccination with Salmonella typhi, whereas CD62L was enriched after systemic (intramuscular) immunization with the same antigen (15). Studies of rotavirus, which selectively infects small intestinal epithelium in patients, found that rotavirus antigen-specific IgA + PBs display high levels of CCR9, CCR10, and α4β7 (1), consistent with the patterns of imprinting in celiac disease as shown here and in a report by Tarlton et al (39).…”

Section: Discussionsupporting

confidence: 89%

“…In general, the representation of memory B cells with different tissue-targeted phenotypes did not correlate or vary substantially with patient/disease class. Long-lived circulating memory cells may even be depleted from the blood by recruitment during active immune responses in tissues (39), potentially balanced by new memory cell generation which would likely follow the initial influx of activated lymphocytes during resolution of the response. In addition to the trafficking receptors we evaluated, memory B cells express CCR6 (41).…”

Section: Discussionmentioning

confidence: 99%

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Trafficking receptor signatures define blood plasmablasts responding to tissue-specific immune challenge

Seong¹,

Lazarus²,

Sutherland³

et al. 2017

JCI Insight

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Trafficking receptor signatures define blood plasmablasts responding to tissue-specific immune challenge

Seong¹,

Lazarus²,

Sutherland³

et al. 2017

JCI Insight

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“…Expansion of plasmablasts was not observed in any of the ON patients in either compartment. The frequency of CD27 high plasmablasts is elevated in several autoimmune diseases 30,31,34,35 and occurs in the diseased tissues where the putative autoantigens are present.…”

Section: Discussionmentioning

confidence: 99%

“…29 An abnormal expansion of CD27 high plasmablasts has been documented in the afflicted compartments of several autoimmune diseases, such as rheumatoid arthritis, 30 Sjogren’s, 31 systemic lupus erythematosus, 32 neuromyelitis optica (NMO), 33 ankylosing spondylitis 34 and pediatric ulcerative colitis. 35 In addition, patients with active systemic lupus erythematosus have greater counts of CD27 high plasmablasts in the periphery than in healthy controls (HCs) or patients with inactive disease, 32,36–39 suggesting these expanding plasmablasts may be contributing to damage associated with these autoimmune diseases.…”

Section: Introductionmentioning

confidence: 99%

Expansion of CD27high plasmablasts in transverse myelitis patients that utilize VH4 and JH6 genes and undergo extensive somatic hypermutation

et al. 2013

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Patients with the autoimmune disease multiple sclerosis (MS) typically present with the clinically isolated syndromes (CIS) transverse myelitis (TM) or optic neuritis (ON). B-cell disturbances have been well documented in patients with MS and CIS patients with ON, but not in CIS patients with TM, despite the fact that these patients have the worst clinical outcome of all CIS types. The goal of this study was to characterize the B-cell populations and immunoglobulin genetics in TM patients. We found a unique expansion of CD27high plasmablasts in both the cerebrospinal fluid and periphery of TM patients that is not present in ON patients. Additionally, plasmablasts from TM patients show evidence for positive selection with increased somatic hypermutation accumulation in VH4+ B cells and receptor editing that is not observed in ON patients. These characteristics unique to TM patients may impact disease severity and progression.

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“…48,77,79,81,83 In patients with active colitis, circulating plasmablasts express high levels of integrin α 4 β 7 and CCR10, compared with patients without colitis. 84 …”

Section: Homing Of Leukocytes To the Lamina Propriamentioning

confidence: 99%

Leukocyte Trafficking to the Small Intestine and Colon

et al. 2016

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Leukocyte trafficking to the small and large intestines is tightly controlled to maintain intestinal immune homeostasis, mediate immune responses, and regulate inflammation. A wide array of chemoattractants, chemoattractant receptors, and adhesion molecules expressed by leukocytes, mucosal endothelium, epithelium, and stromal cells controls leukocyte recruitment and microenvironmental localization in intestine and in the gut-associated lymphoid tissues (GALTs). Naive lymphocytes traffic to the gut-draining mesenteric lymph nodes where they undergo antigen-induced activation and priming; these processes determine their memory/effector phenotypes and imprint them with the capacity to migrate via the lymph and blood to the intestines. Mechanisms of T-cell recruitment to GALT and of T cells and plasmablasts to the small intestine are well described. Recent advances include the discovery of an unexpected role for lectin CD22 as a B-cell homing receptor GALT, and identification of the orphan G-protein–coupled receptor 15 (GPR15) as a T-cell chemoattractant/trafficking receptor for the colon. GPR15 decorates distinct subsets of T cells in mice and humans, a difference in species that could affect translation of the results of mouse colitis models to humans. Clinical studies with antibodies to integrin α4β7 and its vascular ligand mucosal vascular addressin cell adhesion molecule 1 are proving the value of lymphocyte trafficking mechanisms as therapeutic targets for inflammatory bowel diseases. In contrast to lymphocytes, cells of the innate immune system express adhesion and chemoattractant receptors that allow them to migrate directly to effector tissue sites during inflammation. We review the mechanisms for innate and adaptive leukocyte localization to the intestinal tract and GALT, and discuss their relevance to human intestinal homeostasis and inflammation.

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Plasmablast frequency and trafficking receptor expression are altered in pediatric ulcerative colitis

Cited by 19 publications

References 37 publications

Trafficking receptor signatures define blood plasmablasts responding to tissue-specific immune challenge

Trafficking receptor signatures define blood plasmablasts responding to tissue-specific immune challenge

Expansion of CD27high plasmablasts in transverse myelitis patients that utilize VH4 and JH6 genes and undergo extensive somatic hypermutation

Leukocyte Trafficking to the Small Intestine and Colon

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