Apoptotic cell responses in the splenic marginal zone

A paradigm for immunologic reactions to apoptotic antigens with implications for autoimmunity

Tracy L. McGaha, Mikael C.I. Karlsson

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Apoptotic cells drive innate regulatory responses that result in tolerogenic immunity. This is a critical aspect of cell physiology as apoptotic cells expose potentially dangerous nuclear antigens on the surface in apoptotic blebs, and failure in their recognition, phagocytosis, or destruction can cause dramatic autoimmunity in experimental models and is linked to development and progression of systemic pathology in human. The marginal zone is a specialized splenic environment that serves as a transitional site from circulation to peripheral lymphoid structures. The marginal zone serves a key role in trapping of particulates and initiation of innate responses against systemic microbial pathogens. However in recent years, it has become clear the marginal zone is also important for initiation of immune tolerance to apoptotic cells, driving a coordinated response involving multiple phagocyte and lymphocyte subsets. Recent reports linking defects in splenic macrophage function to systemic lupus erythematosus in a manner analogous to marginal zone macrophages in lupus-prone mice provide an impetus to better understand the mechanistic basis of the apoptotic cell response in the marginal zone and its general applicability to apoptotic cell-driven tolerance at other tissue sites. In this review, we discuss immune responses to apoptotic cells in the spleen in general and the marginal zone in particular, the relationship of these responses to autoimmune disease, and comparisons to apoptotic cell immunity in humans.

Original languageEnglish (US)
Pages (from-to)26-43
Number of pages18
JournalImmunological Reviews
Volume269
Issue number1
DOIs
StatePublished - Jan 1 2016

Fingerprint

Autoimmunity
Antigens
Immunity
Macrophages
Cell Physiological Phenomena
Nuclear Antigens
Immune Tolerance
Lymphocyte Subsets
Blister
Phagocytes
Phagocytosis
Systemic Lupus Erythematosus
Autoimmune Diseases
Theoretical Models
Spleen
Pathology

Keywords

  • Apoptosis
  • Autoimmunity
  • B cell
  • Macrophage
  • Marginal zone
  • Tolerance

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Apoptotic cell responses in the splenic marginal zone : A paradigm for immunologic reactions to apoptotic antigens with implications for autoimmunity. / McGaha, Tracy L.; Karlsson, Mikael C.I.

In: Immunological Reviews, Vol. 269, No. 1, 01.01.2016, p. 26-43.

Research output: Contribution to journalArticle

@article{2e983de43a574e0ca42ac6b44f69d806,
title = "Apoptotic cell responses in the splenic marginal zone: A paradigm for immunologic reactions to apoptotic antigens with implications for autoimmunity",
abstract = "Apoptotic cells drive innate regulatory responses that result in tolerogenic immunity. This is a critical aspect of cell physiology as apoptotic cells expose potentially dangerous nuclear antigens on the surface in apoptotic blebs, and failure in their recognition, phagocytosis, or destruction can cause dramatic autoimmunity in experimental models and is linked to development and progression of systemic pathology in human. The marginal zone is a specialized splenic environment that serves as a transitional site from circulation to peripheral lymphoid structures. The marginal zone serves a key role in trapping of particulates and initiation of innate responses against systemic microbial pathogens. However in recent years, it has become clear the marginal zone is also important for initiation of immune tolerance to apoptotic cells, driving a coordinated response involving multiple phagocyte and lymphocyte subsets. Recent reports linking defects in splenic macrophage function to systemic lupus erythematosus in a manner analogous to marginal zone macrophages in lupus-prone mice provide an impetus to better understand the mechanistic basis of the apoptotic cell response in the marginal zone and its general applicability to apoptotic cell-driven tolerance at other tissue sites. In this review, we discuss immune responses to apoptotic cells in the spleen in general and the marginal zone in particular, the relationship of these responses to autoimmune disease, and comparisons to apoptotic cell immunity in humans.",
keywords = "Apoptosis, Autoimmunity, B cell, Macrophage, Marginal zone, Tolerance",
author = "McGaha, {Tracy L.} and Karlsson, {Mikael C.I.}",
year = "2016",
month = "1",
day = "1",
doi = "10.1111/imr.12382",
language = "English (US)",
volume = "269",
pages = "26--43",
journal = "Immunological Reviews",
issn = "0105-2896",
publisher = "Wiley-Blackwell",
number = "1",

}

TY - JOUR

T1 - Apoptotic cell responses in the splenic marginal zone

T2 - A paradigm for immunologic reactions to apoptotic antigens with implications for autoimmunity

AU - McGaha, Tracy L.

AU - Karlsson, Mikael C.I.

PY - 2016/1/1

Y1 - 2016/1/1

N2 - Apoptotic cells drive innate regulatory responses that result in tolerogenic immunity. This is a critical aspect of cell physiology as apoptotic cells expose potentially dangerous nuclear antigens on the surface in apoptotic blebs, and failure in their recognition, phagocytosis, or destruction can cause dramatic autoimmunity in experimental models and is linked to development and progression of systemic pathology in human. The marginal zone is a specialized splenic environment that serves as a transitional site from circulation to peripheral lymphoid structures. The marginal zone serves a key role in trapping of particulates and initiation of innate responses against systemic microbial pathogens. However in recent years, it has become clear the marginal zone is also important for initiation of immune tolerance to apoptotic cells, driving a coordinated response involving multiple phagocyte and lymphocyte subsets. Recent reports linking defects in splenic macrophage function to systemic lupus erythematosus in a manner analogous to marginal zone macrophages in lupus-prone mice provide an impetus to better understand the mechanistic basis of the apoptotic cell response in the marginal zone and its general applicability to apoptotic cell-driven tolerance at other tissue sites. In this review, we discuss immune responses to apoptotic cells in the spleen in general and the marginal zone in particular, the relationship of these responses to autoimmune disease, and comparisons to apoptotic cell immunity in humans.

AB - Apoptotic cells drive innate regulatory responses that result in tolerogenic immunity. This is a critical aspect of cell physiology as apoptotic cells expose potentially dangerous nuclear antigens on the surface in apoptotic blebs, and failure in their recognition, phagocytosis, or destruction can cause dramatic autoimmunity in experimental models and is linked to development and progression of systemic pathology in human. The marginal zone is a specialized splenic environment that serves as a transitional site from circulation to peripheral lymphoid structures. The marginal zone serves a key role in trapping of particulates and initiation of innate responses against systemic microbial pathogens. However in recent years, it has become clear the marginal zone is also important for initiation of immune tolerance to apoptotic cells, driving a coordinated response involving multiple phagocyte and lymphocyte subsets. Recent reports linking defects in splenic macrophage function to systemic lupus erythematosus in a manner analogous to marginal zone macrophages in lupus-prone mice provide an impetus to better understand the mechanistic basis of the apoptotic cell response in the marginal zone and its general applicability to apoptotic cell-driven tolerance at other tissue sites. In this review, we discuss immune responses to apoptotic cells in the spleen in general and the marginal zone in particular, the relationship of these responses to autoimmune disease, and comparisons to apoptotic cell immunity in humans.

KW - Apoptosis

KW - Autoimmunity

KW - B cell

KW - Macrophage

KW - Marginal zone

KW - Tolerance

UR - http://www.scopus.com/inward/record.url?scp=84950110305&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84950110305&partnerID=8YFLogxK

U2 - 10.1111/imr.12382

DO - 10.1111/imr.12382

M3 - Article

VL - 269

SP - 26

EP - 43

JO - Immunological Reviews

JF - Immunological Reviews

SN - 0105-2896

IS - 1

ER -