Complement and non-complement activating functions of C1q: A prototypical innate immune molecule

Abstract

C1q is a versatile innate immune molecule that serves as the initiation subcomponent of the classical complement pathway. In addition, it is also a potent pattern recognition molecule, the versatility of which has fuelled its functional flexibility. C1q recognises an array of self, non-self and altered-self ligands. The broad-spectrum ligand-binding potential of C1q is facilitated by the modular organisation of the heterotrimeric globular head region, its ability to change its conformation in a very subtle way, and the manner in which this ancient molecule appears to have evolved to deal with the different types of ligands. Over recent years, molecules that resemble C1q have been put together to form the C1q family. In this review, we briefly summarise complement-dependent and complement-independent functions of C1q, its cognate receptors and key members of the rapidly growing C1q family.

C1q limits dendritic cell differentiation and activation by engaging LAIR-1

“…Because both gC1q receptors and LAIR-1 are present on freshly isolated monocytes and gC1q has been shown to engage gC1q cellular receptors directly (1,23,24), it is possible that binding of gC1q to gC1q receptors contributes to the avidity of the C1q interaction with LAIR-1 and to the cross-linking of LAIR-1. Notwithstanding, the inhibitory activity prompted by anti-LAIR-1 antibodies that promote LAIR-1 cross-linking indicates that engagement of gC1q is not required for LAIR-1 activation.…”

“…These include facilitating phagocytosis and regulating cellular differentiation, survival, migration, and cytokine secretion (1)(2)(3)(4)(5). An immunosuppressive role for C1q is supported by the high frequency of C1q-deficient individuals who develop systemic lupus erythematosus (SLE) (6).…”

“…Each polypeptide contains a C-terminal globular head region (gC1q) and N-terminal collagen-like Gly-Pro-Hyp (GPO) repeat region (CLR) (9). Several receptors for C1q have been identified, including CD93 (C1qRp), CD35 (CR1), gC1qR (p33), α2β1 integrin, calreticulin (cC1qR), and CD91 (1). Cell-associated receptors described to date for both gC1q and CLR do not exhibit intracellular inhibitory signaling domains, and the identification of C1q receptors on the plasma membrane with intracellular inhibitory signaling capacity has remained elusive.…”

C1q as a unique player in angiogenesis with therapeutic implication in wound healing

“…C1q is well known to activate the classical pathway and to act as a defense molecule favoring the removal of infectious agents, apoptotic cells, and immune complexes (16). In Significance C1q is a well-known initiator of the complement classical pathway and interacts with several immune and nonimmune cells inducing complement activation-independent functions.…”

iTRAQ-based quantitative proteomic analysis reveals potential early diagnostic markers of clear-cell Renal cell carcinoma

“…In addition, we found that the expression of the 11 differentially expressed serum proteins (C1QB, C1QC, ANXA1, LYZ, CP, ACT, ZG16B, S100A8, S100A9, SERPINA4, and LUM) was associated with the RCC tumor stage and grade. Functionally, C1QB and C1QC are complement subcomponent subunits (16) and are related to antibody-dependent and -independent immune responses in the human body (17). They are able to induce apoptosis of prostate cancer cells by targeting the tumor suppressor WWOX and hampering cell adhesion via a mechanism which is still unknown (18).…”