Abstract
Myeloid C‐type lectin receptors (CLRs), which consist of an extracellular carbohydrate recognition domain and intracellular signal transducing motif such as the immunoreceptor tyrosine‐based activation motif (ITAM) or immunoreceptor tyrosine‐based inhibitory motif (ITIM), are innate immune receptors primarily expressed on myeloid lineage cells such as dendritic cells (DCs) and Mϕs. CLRs play important roles in host defense against infection by fungi and bacteria by recognizing specific carbohydrate components of these pathogens. However, these immune receptors also make important contributions to immune homeostasis of mucosa and skin in mammals by recognizing components of microbiota, as well as by recognizing self‐components such as alarmins from dead cells and noncanonical non‐carbohydrate ligands. CLR deficiency not only induces hypersensitivity to infection, but also causes dysregulation of muco‐cutaneous immune homeostasis, resulting in the development of allergy, inflammation, autoimmunity, and tumors. In this review, we introduce recent discoveries regarding the roles of myeloid CLRs in the immune system exposed to the environment, and discuss the roles of these lectin receptors in the development of colitis, asthma, psoriasis, atopic dermatitis, and cancer. Although some CLRs are suggested to be involved in the development of these diseases, the function of CLRs and their ligands still largely remain to be elucidated.
Highlights
C-type lectins (CTLs) are one of pattern recognition receptors (PRRs) that recognize pathogen-associated molecular patterns (PAMPs) of pathogens
DECTIN-1 on CD11b+ dendritic cell (DC) binds to components of house dust mite (HDM) extracts and modulates both Th2- and Th17related immune responses; the production of IL-5, IL-13, and IL-17A, as well as chemokines CCR7, CCL3, and CCL4, is reduced in Clec7a–/– mice upon HDM exposure,[65] the ligands for DECTIN-1
It is likely that various innate immune receptors such as TLRs and CTL receptor (CLR) expressed on the cell surface of LCs and DCs of the skin recognize PAMPs of bacteria and fungi, as well as alarmins derived from dying cells, and induce cytokines and chemokines including IL36α, IL-23, IL-1β, and CCL20
Summary
C-type lectins (CTLs) are one of pattern recognition receptors (PRRs) that recognize pathogen-associated molecular patterns (PAMPs) of pathogens. Genes encoding other myeloid CLRs, such as DC-SIGN (human Chr. 19) and its mouse homologue SIGNR3 (mouse Chr. 8), LANGERIN, MGL, MDL-1, DCAL-1, MR, and Dec-205 map to other chromosomes These molecules are expressed as membrane proteins in myeloid cells including monocytes, Mφs, and dendritic cells (DCs) (Table 1). Many CLRs encoded in the Dectin-1 and Dectin-2 cluster loci contain ITAM or ITIM in the cytoplasmic domain, suggesting that they transduce signals that regulate cellular function. Some molecules, such as DCAR2, DECTIN-2, MCL, and MINCLE, have no ITAM but form a complex with ITAM-containing FcRγ or DAP10/12 to transduce signals. In this review, we will discuss the roles of myeloid CLRs in the development of diseases of the skin and mucoepithelial tissues as well as in the development of tumors
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