Critical role of integrin CD11c in splenic dendritic cell capture of missing-self CD47 cells to induce adaptive immunity

J Wu, H Wu, J An, CM Ballantyne… - Proceedings of the …, 2018 - National Acad Sciences
J Wu, H Wu, J An, CM Ballantyne, JG Cyster
Proceedings of the National Academy of Sciences, 2018National Acad Sciences
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 …
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.
National Acad Sciences