Dendritic cell-T cell circuitry in health and changes in inflammatory bowel disease and its treatment
File(s)
Accepted version
Published version
Author(s)
Knight, SC
Type
Journal Article
Abstract
Abstract
Background:
Dendritic, antigen-presenting cells (DCs) determine not only whether lymphocytes produce different types of immune response but also tissue-homing profiles of lymphocytes they stimulate. For example, in health, mucosal
DC stimulate T cells focused to home to the mucosa; DC/T-cell circuitry thus targets immune responses to specific tissue locations. Therapies being introduced for inflammatory bowel disease (IBD) include antibodies to gut-homing molecules such as α4β7 (Vedolizumab) used ostensibly to block
gut-homing lymphocytes. However, such lymphocytes are dependent on the tissue specificity of DC that stimulated them.
Key Messages:
In health, blood DCs have the potential to home to multiple tissues including gut (α4β7+) and skin (CLA+). DCs have become gut-specific within the intestinal
microenvironment stimulated partially by local retinoid to express α4β7 (mucosal homing marker) and/or CCR9 (ileal homing marker) in the absence of skin-specific indicators. They spread veiled extensions, sample their environment,
acquire/process antigens, produce cytokines and initiate innate immunity. Myeloid DC also traffic to draining lymph nodes where compartmentalization of adaptive immune responses is determined by DCs from the site of antigen expo-
sure which dictate the homing profiles of lymphocytes they stimulate. In IBD, changes in homing/activation of gut DCs stimulate T-cells, and also, greater gut specificity and activation of blood DC reflect site and activity of disease. Homing
potential of DC can be modulated toward mucosa or skin by vitamins A and D, respectively. Infliximab or interleukin-6 can divert homing profiles toward skin, perhaps predisposing to skin involvement in IBD. Probiotic bacteria or their
products can also change homing profiles of gut DC toward skin homing and away from gut.
Conclusions:
In conclusion, development of gut focused inflammation and its treatment
relies on changes in DC tissue specificity; therefore, removal
or diversion of gut-homing DC as well as T-cells is likely to be
critical in prevention of gut-focused inflammation in IBD.
Background:
Dendritic, antigen-presenting cells (DCs) determine not only whether lymphocytes produce different types of immune response but also tissue-homing profiles of lymphocytes they stimulate. For example, in health, mucosal
DC stimulate T cells focused to home to the mucosa; DC/T-cell circuitry thus targets immune responses to specific tissue locations. Therapies being introduced for inflammatory bowel disease (IBD) include antibodies to gut-homing molecules such as α4β7 (Vedolizumab) used ostensibly to block
gut-homing lymphocytes. However, such lymphocytes are dependent on the tissue specificity of DC that stimulated them.
Key Messages:
In health, blood DCs have the potential to home to multiple tissues including gut (α4β7+) and skin (CLA+). DCs have become gut-specific within the intestinal
microenvironment stimulated partially by local retinoid to express α4β7 (mucosal homing marker) and/or CCR9 (ileal homing marker) in the absence of skin-specific indicators. They spread veiled extensions, sample their environment,
acquire/process antigens, produce cytokines and initiate innate immunity. Myeloid DC also traffic to draining lymph nodes where compartmentalization of adaptive immune responses is determined by DCs from the site of antigen expo-
sure which dictate the homing profiles of lymphocytes they stimulate. In IBD, changes in homing/activation of gut DCs stimulate T-cells, and also, greater gut specificity and activation of blood DC reflect site and activity of disease. Homing
potential of DC can be modulated toward mucosa or skin by vitamins A and D, respectively. Infliximab or interleukin-6 can divert homing profiles toward skin, perhaps predisposing to skin involvement in IBD. Probiotic bacteria or their
products can also change homing profiles of gut DC toward skin homing and away from gut.
Conclusions:
In conclusion, development of gut focused inflammation and its treatment
relies on changes in DC tissue specificity; therefore, removal
or diversion of gut-homing DC as well as T-cells is likely to be
critical in prevention of gut-focused inflammation in IBD.
Date Issued
2016-03-01
Date Acceptance
2015-12-01
Citation
Digestive Diseases, 2016, 34 (1-2), pp.51-57
ISSN
1421-9875
Publisher
Karger
Start Page
51
End Page
57
Journal / Book Title
Digestive Diseases
Volume
34
Issue
1-2
Copyright Statement
© 2016 The Author(s). Th is article is licensed under the Creative Commons Attribution NonCommercial-No Derivatives
4.0 International License (CC BYNC-ND)
(http://www.karger.com/Services/OpenAccessLicense).
Usage and distribution for commercial purposes as well as any distribution
of modified material requires written permission.
4.0 International License (CC BYNC-ND)
(http://www.karger.com/Services/OpenAccessLicense).
Usage and distribution for commercial purposes as well as any distribution
of modified material requires written permission.
Sponsor
Biotechnology and Biological Sciences Research Cou
Grant Number
PR5858-000-A
Subjects
Gastroenterology & Hepatology
1103 Clinical Sciences
Publication Status
Published