Primate Monocytes - CD14, CD16 - Ziegler-Heitbrock

Upregulated Macrophage-inducible C-type Lectin on Intermediate Monocyte Facilitates T helper 17 cell Differentiation in Systemic Lupus Erythematosus.

Abstract

Pattern recognition receptors are crucial for autoimmune responses. While C-type lectins play important roles in immune responses, their involvement in systemic lupus erythematosus (SLE) pathogenesis remains less understood. To investigate this, we utilized Gene Expression Omnibus data for bioinformatics analyses and obtained peripheral blood samples from SLE patients to study the expression, functions, and potential mechanisms of macrophage-inducible C-type lectin (Mincle). The results indicated that the C-type lectin receptor signaling pathway is involved in SLE initiation, with Mincle mRNA levels significantly upregulated in SLE. Specifically, upregulated Mincle was observed on intermediate monocytes (CD14+CD16+) from SLE patients. The increased Mincle expression among intermediate monocytes was associated with elevated serum immunoglobulin G and kappa-light chain in SLE. Moreover, the intermediate monocytes from SLE promoted T helper 17 (Th17) differentiation. In THP-1 cells, Mincle deficiency reduced the differentiation of CD4+ naive T cells towards Th17, whereas Mincle overexpression in THP-1 and U937 cells facilitated differentiation towards Th1 and Th17. In conclusion, upregulated Mincle on circulating intermediate monocytes facilitates T cell differentiation toward Th17, thereby aggravating systemic inflammation and promoting SLE progression.