Wu et al. found that CD11c (integrin αX), the defining marker for dendritic cells (DCs), and its partner, integrin β2 (Itgb2), were critical for splenic cDC2 capture of cells deficient in self-marker CD47 and for DC activation in a manner dependent on integrin-signaling regulator Talin1. In vivo, Talin1-deficient cDC2s were ineffective in inducing TFH and T cell-dependent B cell responses to cells lacking CD47. CD11b (integrin αM), which is also expressed on cDC2s, was not required for capture of CD47-deficient cells, but partially compensated for the absence of CD11c. The activating receptor for the CD11c/Itgb2 complex is unknown.
CD11c, also known as integrin alpha X, is the most widely used defining marker for dendritic cells (DCs). CD11c can bind complement iC3b and mediate phagocytosis in vitro, for which it is also referred to as complement receptor 4. However, the functions of this prominent marker protein in DCs, especially in vivo, remain poorly defined. Here, in the process of studying DC activation and immune responses induced by cells lacking self-CD47, we found that DC capture of CD47-deficient cells and DC activation was dependent on the integrin-signaling adaptor Talin1. Specifically, CD11c and its partner Itgb2 were required for DC capture of CD47-deficient cells. CD11b was not necessary for this process but could partially compensate in the absence of CD11c. Mice with DCs lacking Talin1, Itgb2, or CD11c were defective in supporting T-cell proliferation and differentiation induced by CD47-deficient cell associated antigen. These findings establish a critical role for CD11c in DC antigen uptake and activation in vivo. They may also contribute to understanding the functional mechanism of CD47-blockade therapies.
Author Info: (1) Department of Microbiology and Immunology, University of California, San Francisco, CA 94143. (2) Department of Medicine, Baylor College of Medicine, Houston, TX 77030. Departm
Author Info: (1) Department of Microbiology and Immunology, University of California, San Francisco, CA 94143. (2) Department of Medicine, Baylor College of Medicine, Houston, TX 77030. Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030. (3) Department of Microbiology and Immunology, University of California, San Francisco, CA 94143. (4) Department of Medicine, Baylor College of Medicine, Houston, TX 77030. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030. Center for Cardiovascular Disease Prevention, Methodist DeBakey Heart and Vascular Center, Houston Methodist Hospital and Baylor College of Medicine, Houston, TX 77030. (5) Department of Microbiology and Immunology, University of California, San Francisco, CA 94143; jason.cyster@ucsf.edu. Howard Hughes Medical Institute, University of California, San Francisco, CA
