CD47 Blockade Leads to Chemokine-Dependent Monocyte Infiltration and Loss of B Cells from the Splenic Marginal Zone-Reference-Cited by-同舟云学术

CD47 Blockade Leads to Chemokine-Dependent Monocyte Infiltration and Loss of B Cells from the Splenic Marginal Zone

Published:2022-03-15 Issue:6 Volume:208 Page:1371-1377
ISSN:0022-1767
Container-title:The Journal of Immunology
language:en
Short-container-title:

Author:

Yiu Ying Ying¹²^ORCID,Hansen Paige S.¹³,Torrez Dulgeroff Laughing Bear¹,Blacker Grace¹^ORCID,Myers Lara⁴^ORCID,Galloway Sarah¹^ORCID,Gars Eric⁵,Colace Olivia¹,Mansfield Paul¹,Hasenkrug Kim J.⁴^ORCID,Weissman Irving L.¹⁵⁶⁷,Tal Michal Caspi¹³^ORCID

Affiliation:

1. *Institute for Stem Cell Biology and Regenerative Medicine and the Ludwig Cancer Center, Stanford University School of Medicine, Stanford, CA;

2. †Immunology Program, Stanford University, Stanford, CA;

3. ‡Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA;

4. §Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT;

5. ¶Department of Pathology, Stanford University School of Medicine, Stanford, CA;

6. ‖Ludwig Center for Cancer Stem Cell Research and Medicine, Stanford University School of Medicine, Stanford, CA; and

7. #Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA

Abstract

Abstract CD47 is an important innate immune checkpoint through its interaction with its inhibitory receptor on macrophages, signal-regulatory protein α (SIRPα). Therapeutic blockade of CD47–SIRPα interactions is a promising immuno-oncology treatment that promotes clearance of cancer cells. However, CD47–SIRPα interactions also maintain homeostatic lymphocyte levels. In this study, we report that the mouse splenic marginal zone B cell population is dependent on intact CD47–SIRPα interactions and blockade of CD47 leads to the loss of these cells. This depletion is accompanied by elevated levels of monocyte-recruiting chemokines CCL2 and CCL7 and infiltration of CCR2+Ly6Chi monocytes into the mouse spleen. In the absence of CCR2 signaling, there is no infiltration and reduced marginal zone B cell depletion. These data suggest that CD47 blockade leads to clearance of splenic marginal zone B cells.

Funder

Virginia and D.K. Ludwig Fund for Cancer Research

Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation

Division of Intramural Research, National Institute of Allergy and Infectious Diseases

Fairbairn Family Foundation

Bay Area Lyme Foundation

National Science Foundation

HHS | National Institutes of Health

Stanford University

Publisher

The American Association of Immunologists

Subject