Adhesion GPCRs as Modulators of Immune Cell Function

  • Jörg HamannEmail author
  • Cheng-Chih Hsiao
  • Chang Sup Lee
  • Kodi S. Ravichandran
  • Hsi-Hsien LinEmail author
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 234)

Graphical Abstract


Immune cells express several adhesion G protein-coupled receptors (aGPCRs), including the ADGRE subfamily members EMR1 (F4/80, ADGRE1), EMR2 (ADGRE2), EMR3 (ADGRE3), EMR4 (FIRE, ADGRE4), and CD97 (ADGRE5), the ADGRB subfamily member BAI1 (ADGRB1), and the ADGRG subfamily members GPR56 (ADGRG1), GPR97 (Pb99, ADGRG3), and GPR114 (ADGRG5). Expression of these molecules in hematopoietic stem and progenitor cells, monocytes/macrophages (Mφs), dendritic cells, granulocytes, and lymphocytes depends on lineage diversification and maturation, making them suitable markers for individual leukocyte subsets (e.g., F4/80 on mouse Mφs). Recent studies revealed intriguing activities of aGPCRs in tolerance induction (EMR1), granulopoiesis (CD97), engulfment of apoptotic cells and bacteria (BAI1), hematopoietic stem cell formation (GPR56), and control of cytotoxicity (GPR56). Here, we review these findings and discuss their biological and translational implications.


Adhesion GPCRs Immunity Macrophages Granulocytes T cells Phagocytosis 



Seven transmembrane




ATP-binding cassette transporter


Anterior chamber-associated immune deviation




Acute myeloid leukemia


Brain-specific angiogenesis inhibitor


Blood dendritic cell antigen


C-terminal fragment


Dendritic cell


Epidermal growth factor


Engulfment and cell motility


EGF-like module-containing mucin-like hormone receptor-like


GPCR autoproteolysis inducing


Guanine nucleotide exchange factor


G protein-coupled receptor


GPCR proteolysis site


High-density lipoprotein


Hormone receptor motif


Hematopoietic stem and progenitor cell






Low-density lipoprotein




Monoclonal antibody



Natural killer


N-terminal fragment




Reactive oxygen species


Systemic inflammatory response syndrome


Tumor growth factor


Tumor necrosis factor


Regulatory T


Thrombospondin type 1 repeat



We thank the members of our laboratories for generating a large part of the data discussed in this chapter. This work was supported by grants to J.H. from the Deutsche Forschungsgemeinschaft (Research Unit 2149) and the Thyssen Foundation (2015-00387), to K.S.R. from the National Institutes of Health, USA (GM064709, HD074981, and MH096484), and to H.H.L. from the Ministry of Science and Technology, Taiwan (MOST-104-2320-B-182-035-MY3) and the Chang Gung Memorial Hospital (CMRPD1C0633, CMRPD1D0072-3, and CMRPD1D0392).

Author Contributions J.H., C.C.H., H.H.L., C.S.L., and K.S.R. wrote the manuscript.

Competing Financial Interests The authors declare no competing financial interests.


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Copyright information

© Springer International Publishing AG 2016

Authors and Affiliations

  1. 1.Department of Experimental Immunology, K0-144, Academic Medical CenterUniversity of AmsterdamAmsterdamThe Netherlands
  2. 2.Department of Microbiology, Immunology, and Cancer BiologyUniversity of VirginiaCharlottesvilleUSA
  3. 3.Department of Microbiology and ImmunologyChang Gung UniversityTao-YuanTaiwan
  4. 4.Chang Gung Immunology Consortium and Department of Anatomic PathologyChang Gung Memorial Hospital-LinkouTao-YuanTaiwan

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