Figure 4.

Functions of collectins in skin immune homeostasis. Collectins are similar in structure in terms of their carbohydrate recognition domains, collagen-like, and N-terminal regions. MBL and CL-K1 recognize microorganisms and activate the lectin pathway to clear pathogens. SP-A and SP-D can bind to microorganisms directly and cause aggregation. CL-L1 might initiate the lectin pathway by forming CL-LK with CL-K1. MBL, SP-A, and SP-D can recognize DNA from apoptotic cells and mediate the uptake of apoptotic cells. SP-A and SP-D also suppress apoptotic cell clearance by binding SIRP-α on macrophages (black arrows). MBL promotes keratinocytes to produce chemokine (C-X-C motif) ligand 1 to increase neutrophil infiltration. Surfactant proteins might induce the production of TNF-α via macrophages. SP-A and SP-D can bind to SIRP-α on macrophages and epithelia through their globular heads to suppress inflammation (black arrows). CL-K1 may modulate the production of IL-6 and IL-10 by fibroblasts. CL-K1 and CL-L1 may influence the function of melanocytes by affecting the immigration of neural crest cells. Clearance of pathogens rely on the participation of inflammatory cells and cytokines, and inflammatory responses lead to immune cells undergoing apoptosis. In reverse, accumulation of apoptotic cells can cause inflammation. And dysfunction of skin caused by inflammation results in inability of pathogens clearance. Thus, skin infectious diseases, inflammatory diseases and autoimmune diseases interact tightly with each other. The solid lines represent known functions, while dashed lines represent speculations.