C-type lectin domain family 4 member D

Definition

Calcium-dependent lectin that acts as a pattern recognition receptor (PRR) of the innate immune system: recognizes damage-associated molecular patterns (DAMPs) of pathogen-associated molecular patterns (PAMPs) of bacteria and fungi. The PAMPs include alpha-mannans on C.albicans hypheas and mycobacterial trehalose 6,6'-dimycolate (TDM). Interacts with signaling adapter Fc receptor gamma chain/FCER1G, likely via CLEC4E, to form a functional complex in myeloid cells (By similarity). Binding of mycobacterial TDM or C.albicans alpha-mannans to this receptor complex leads to phosphorylation of the immunoreceptor tyrosine-based activation motif (ITAM) of FCER1G, triggering activation of SYK, CARD9 and NF-kappa-B, consequently driving maturation of antigen-presenting cells and shaping antigen-specific priming of T-cells toward effector T-helper 1 and T-helper 17 cell subtypes. The heterodimer formed with CLEC6A is active against fungal infection. Functions as an endocytic receptor. May be involved in antigen uptake at the site of infection, either for clearance of the antigen, or for processing and further presentation to T-cells.

References:

[1]. Ignacio Arce, et al. The human C-type lectin CLECSF8 is a novel monocyte/macrophage endocytic receptor. Eur J Immunol. 2004 Jan;34(1):210-20. [Content Brief]

[2]. Yasunobu Miyake, et al. C-type lectin MCL is an FcRγ-coupled receptor that mediates the adjuvanticity of mycobacterial cord factor. Immunity. 2013 May 23;38(5):1050-62. [Content Brief]

[3]. Le-Le Zhu, et al. C-type lectin receptors Dectin-3 and Dectin-2 form a heterodimeric pattern-recognition receptor for host defense against fungal infection. Immunity. 2013 Aug 22;39(2):324-34. [Content Brief]

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