Periductal Induction of High Endothelial Venule-Like Vessels in Type 1 Autoimmune Pancreatitis

Abstract

Objectives: Type 1 autoimmune pancreatitis (AIP) is histologically characterized by dense lymphoplasmacytic infiltration and marked storiform fibrosis, manifestations associated with pancreatic ducts. Such periductal lymphocyte recruitment is thought to be elicited by dysregulation of mechanisms governing physiological lymphocyte homing. The present study was undertaken to determine whether vascular addressins including peripheral lymph node addressin (PNAd) and mucosal addressin cell adhesion molecule 1 (MAdCAM-1) play a role in type 1 AIP histogenesis.Methods: Tissue sections of type 1 AIP and tumor-associated non-AIP chronic pancreatitis, as well as normal pancreas, were subjected to immunohistochemical analysis using vascular addressin-related antibodies.Results: The number of periductal MECA-79 + high endothelial venule (HEV)-like vessels was increased in type 1 AIP relative to that seen in non-AIP chronic pancreatitis, while the number of MAdCAM-1 + HEV-like vessels did not differ between the two conditions. MECA-79 antigens are expressed on duct-forming epithelial cells not only in pancreas but also in salivary glands, which often harbor extrapancreatic lesions in type 1 AIP.Conclusions: Type 1 AIP can be characterized by periductal induction of MECA-79 + HEV-like vessels.MECA-79 + 6-sulfo sialyl Lewis X-related carbohydrate antigens expressed on duct-forming epithelial 3 cells could be associated with type 1 AIP pathogenesis.

Lymphocyte recruitment via high endothelial venules in lymphoid stroma of Warthin’s tumour

“…26 In that study, we found that MECA-79 antigens were expressed not only on HEV-like vessels but also on exocrine duct-forming epithelium in both pancreases and salivary glands. 26 In that study, we found that MECA-79 antigens were expressed not only on HEV-like vessels but also on exocrine duct-forming epithelium in both pancreases and salivary glands.…”

Lymphocyte ‘homing’ and chronic inflammation

“…Its initial phase is a morphological and functional change of postcapillary venules into HEV‐like vessels in order to augment lymphocyte migration. As discussed below, endothelial cells in such pathologic conditions express several distinct adhesion molecules involved in lymphocyte recruitment …”

“…It is noteworthy that, in chronic abdominal inflammation, expression levels of MAdCAM‐1 on HEV‐like vessels is also upregulated by proinflammatory cytokines such as TNF‐α, interleukin (IL)‐1β and IL‐10 . In addition, these MAdCAM‐1 proteins can be glycosylated with 6‐sulfo sialyl Lewis X‐capped carbohydrates at its mucin‐like domains as abdominal inflammation develops . Thus, lymphocyte tethering and rolling in abdominal inflammation is mediated by two independent molecular interactions: one between MAdCAM‐1 and low‐affinity α 4 β 7 integrin, and the other between 6‐sulfo sialyl Lewis X‐capped glycans and L‐selectin.…”

“…Lymphocyte recruitment and consequent formation of tertiary lymphoid tissues occurs in most chronic inflammatory disorders, and in fact, is implicated in rheumatoid arthritis, Helicobacter pylori gastritis, inflammatory bowel disease (IBD) including ulcerative colitis and Crohn disease, autoimmune pancreatitis and sclerosing sialadenitis, according to the morphological, immunohistochemical and molecular‐biological analysis of the activity of HEV‐like vessels in these inflammatory conditions as discussed below.…”

“…In chronic inflammation, resultant migration of circulating lymphocytes is required to eliminate pathogenic microorganisms or neoplastic cells, even if the inflamed sites are outside of lymphoid tissue. In these cases, venular endothelial cells at inflamed sites upregulates vascular addressin expression and become taller, and venules begin to resemble HEVs . Consequently, lymphocytes recognize these HEV‐like vessels in inflamed tissue as a second target and thus ‘home’ to them, employing mechanisms used in physiological lymphocyte migration.…”