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Functional role of intestinal dendritic cells in mucosal IgA induction

Nakawesi, Joy (2016) MOBT01 20161
Degree Projects in Molecular Biology
Abstract
During steady state, the intestinal immune system functions to maintain the bowel’s physiological function in the face of constant bombardment by environmental materials (potentially infectious agents, commensal bacteria and foreign proteins). Immune responses thus maintain a delicate balance between immunogenicity against harmful invading pathogens and tolerance of the harmless diet and commensal microbiota so as to preserve the health and integrity of the epithelium that has the principle function of digesting and absorbing nutrients. Intestinal conventional dendritic cells (DCs) are thought to be critical in the ‘decision’ of whether to mount tolerogenic or protective immune responses and thus play a critical role in the regulation of... (More)
During steady state, the intestinal immune system functions to maintain the bowel’s physiological function in the face of constant bombardment by environmental materials (potentially infectious agents, commensal bacteria and foreign proteins). Immune responses thus maintain a delicate balance between immunogenicity against harmful invading pathogens and tolerance of the harmless diet and commensal microbiota so as to preserve the health and integrity of the epithelium that has the principle function of digesting and absorbing nutrients. Intestinal conventional dendritic cells (DCs) are thought to be critical in the ‘decision’ of whether to mount tolerogenic or protective immune responses and thus play a critical role in the regulation of the adaptive immune responses. It is well established that secretory IgA is a major component of the epithelial barrier and plays a pivotal role in maintaining intestinal homeostasis. Here, we address the functional role of a specific DC subset, namely the IRF8-dependent (CD103+CD11b-) DC, in regulating the induction of mucosal IgA production by B cells during steady state. We show that mice lacking the IRF8-dependent DCs have increased numbers of B cells particularly in the intestinal draining mesenteric lymph nodes (MLNs). In summary, our results suggest a previously unappreciated role of the IRF8-dependent DCs in regulating mucosal IgA induction during steady state. This can add to an understanding of how, when, and where specific mucosal antibody responses are induced, which may impact the design of better mucosal adjuvants. (Less)
Popular Abstract
During steady state, the intestinal immune system functions to maintain the bowel’s physiological function in the face of constant bombardment by environmental materials (potentially infectious agents, commensal bacteria and foreign proteins). Immune responses thus maintain a delicate balance between immunogenicity against harmful invading pathogens and tolerance of the harmless diet and commensal microbiota so as to preserve the health and integrity of the epithelium that has the principle function of digesting and absorbing nutrients.

Intestinal conventional dendritic cells (DCs), are immune cells that constantly survey around the intestine picking up environmental materials. They present these materials to other immune cells (e.g. B... (More)
During steady state, the intestinal immune system functions to maintain the bowel’s physiological function in the face of constant bombardment by environmental materials (potentially infectious agents, commensal bacteria and foreign proteins). Immune responses thus maintain a delicate balance between immunogenicity against harmful invading pathogens and tolerance of the harmless diet and commensal microbiota so as to preserve the health and integrity of the epithelium that has the principle function of digesting and absorbing nutrients.

Intestinal conventional dendritic cells (DCs), are immune cells that constantly survey around the intestine picking up environmental materials. They present these materials to other immune cells (e.g. B cells) that are more efficient at responding to these materials and provide long-lasting immunity (Adaptive immunity). DCs are thus, thought to be critical in the ‘decision’ of whether to mount tolerogenic or protective immune responses and thus play a critical role in the regulation of the adaptive immune responses. Different types of these DCs are thought to drive different arms of the immune system, with a consequence for the barrier integrity of the intestine. It is well established that secretory IgA, an antibody that plays a critical role in immune function at mucosal surfaces, is a major component of the intestinal epithelial barrier and plays a pivotal role in the maintenance of intestinal immune balance. Here, we address the functional role of one specific DC subset in regulating the induction of mucosal IgA production by B cells during steady state conditions (in absence of infection).

We show that mice lacking our DC subset of interest have increased numbers of B cells, the cells that make antibody, in general. B cells that have acquired the ability to produce IgA are also elevated in numbers in these mice. The effect of the absence of the DC subset on B cells is particularly strong in the lymph nodes draining the intestine, but not in the peyer’s patches (lymphoid aggregates directly on the intestine) and spleen. We also show that the accumulation of B cells in the draining lymph nodes is dendritic cell dependent and we hypothesize that this might be due to an impaired ability of the B cells to home to the intestine.

In summary, our results suggest a previously unappreciated role for a specific subset of dendritic cells in regulating mucosal IgA induction and polarization of B cell-driven immunity during steady state. This can add to an understanding of how, when, and where specific mucosal antibody responses are induced, which may impact the design of better mucosal adjuvants.

Advisor: Katharina Lahl
Co-Advisor: William Agace
Biomedical Centre, Immunology section
Department of Experimental Medical Sciences, Lund University.
Master´s Degree Project 60 credits in Molecular Biology (General) 2016.
Department of Biology, Lund University. (Less)
Please use this url to cite or link to this publication:
author
Nakawesi, Joy
supervisor
organization
course
MOBT01 20161
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
8876764
date added to LUP
2016-06-02 16:01:28
date last changed
2016-06-02 16:01:28
@misc{8876764,
  abstract     = {During steady state, the intestinal immune system functions to maintain the bowel’s physiological function in the face of constant bombardment by environmental materials (potentially infectious agents, commensal bacteria and foreign proteins). Immune responses thus maintain a delicate balance between immunogenicity against harmful invading pathogens and tolerance of the harmless diet and commensal microbiota so as to preserve the health and integrity of the epithelium that has the principle function of digesting and absorbing nutrients. Intestinal conventional dendritic cells (DCs) are thought to be critical in the ‘decision’ of whether to mount tolerogenic or protective immune responses and thus play a critical role in the regulation of the adaptive immune responses. It is well established that secretory IgA is a major component of the epithelial barrier and plays a pivotal role in maintaining intestinal homeostasis. Here, we address the functional role of a specific DC subset, namely the IRF8-dependent (CD103+CD11b-) DC, in regulating the induction of mucosal IgA production by B cells during steady state. We show that mice lacking the IRF8-dependent DCs have increased numbers of B cells particularly in the intestinal draining mesenteric lymph nodes (MLNs). In summary, our results suggest a previously unappreciated role of the IRF8-dependent DCs in regulating mucosal IgA induction during steady state. This can add to an understanding of how, when, and where specific mucosal antibody responses are induced, which may impact the design of better mucosal adjuvants.},
  author       = {Nakawesi, Joy},
  language     = {eng},
  note         = {Student Paper},
  title        = {Functional role of intestinal dendritic cells in mucosal IgA induction},
  year         = {2016},
}