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Role of SLAM-Associated Protein in the Pathogenesis of Autoimmune Diseases and Immunological Disorders

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Archivum Immunologiae et Therapiae Experimentalis Aims and scope

Abstract

Signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) is an adaptor molecule containing a Src homology 2 (SH2) domain. SAP is expressed in T cells and natural killer (NK) cells and binds to the cytoplasmic domains of SLAM family receptors, resulting in the subsequent recruitment of Fyn. The SAP (SH2D1A) gene is located on the X chromosome and is responsible for X-linked lymphoproliferative disease, characterized by higher susceptibility to Epstein-Barr virus infection. The SAP-mediated signal is not only essential for the development of NKT cells, i.e. unconventional CD1d-restricted T cells with invariant Vα14 T cell receptors, but also for the regulation of the function of NK cells and conventional T cells. The role of SAP-mediated signaling in the induction of autoimmune diseases has been analyzed using animal models such as lupus, hepatitis, and graft-versus-host disease and is considered important in their pathogenesis in humans. In this review we highlight the current findings on SAP-mediated signaling in hematopoietic cells and discuss its importance in autoimmune diseases and immunological disorders.

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Abbreviations

SLAM:

Signaling lymphocytic activation molecule

SAP:

SLAM-associated protein

XLP:

X-linked lymphoproliferative disease

NK:

Natural killer

EBV:

Epstein-Barr virus

GVHD:

Graft-versus-host disease

Ig:

Immunoglobulin

ITSM:

Immunoreceptor tyrosine-based switching motif

DC:

Dendritic cell

SNP:

Single-nucleotide polymorphism

SH2:

Src homology 2

EAT-2:

Ewing’s sarcoma-activated transcript-2

ERT:

EAT-2-related transducer

AICD:

Activation-induced cell death

MR-1:

MHC-related 1

MAIT:

Mucosal-associated invariant T

XIAP:

X-linked inhibitor of apoptosis

SLE:

Systemic lupus erythematosus

RA:

Rheumatoid arthritis

FasL:

Fas ligand

ConA:

Concanavalin A

MHC:

Major histocompatibility complex

mHC:

Minor histocompatibility complex

BMT:

Bone marrow transplantation

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Acknowledgments

We thank Dr. Hiroyuki Nishimura (Wakayama Medical University) for fruitful discussions, Ms Fumiko Date, Dr. Izumi Kaneko, Mr. Koichi Kikuchi, Mr. Yuichi Kitagawa, Dr. Yusuke Okubo, Ms Naoko Shibata, Mr. Kaname Uchida, and Ms Naomi Yamaki (Tohoku University) for providing technical assistance for the study at Tohoku University, and Ms Noriko Fujisawa and Ms Emi Yura (Tohoku University) for secretarial assistance. The study at Tohoku University was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Science, Sports, and Culture of Japan to Hiroshi Furukawa (no. 16790221) and Masao Ono (nos. 16390113, 19390108, and 19659096). This paper is dedicated to the memory of Dr. Hiroaki Komori.

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Authors and Affiliations

  1. Department of Pathology, Tohoku University Graduate School of Medicine, Seiryo-machi 2-1, Aoba-ku, Sendai, 980-8575, Japan

    Hiroshi Furukawa, Hiroshi Kitazawa & Masao Ono

  2. Department of Rheumatology, Clinical Research Center for Allergy and Rheumatology, Sagamihara National Hospital, National Hospital Organization, Sagamihara, Japan

    Hiroshi Furukawa & Shigeto Tohma

  3. Department of Pathology, Ehime University Graduate School of Medicine, Toon, Japan

    Masato Nose

Authors
  1. Hiroshi Furukawa
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  2. Shigeto Tohma
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  3. Hiroshi Kitazawa
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  4. Hiroaki Komori
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  5. Masato Nose
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  6. Masao Ono
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Corresponding author

Correspondence to Hiroshi Furukawa.

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Hiroaki Komori: deceased.

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Furukawa, H., Tohma, S., Kitazawa, H. et al. Role of SLAM-Associated Protein in the Pathogenesis of Autoimmune Diseases and Immunological Disorders. Arch. Immunol. Ther. Exp. 58, 37–44 (2010). https://doi.org/10.1007/s00005-009-0060-7

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  • DOI: https://doi.org/10.1007/s00005-009-0060-7

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