Monocytes are a type of white blood cell (leukocytes). They are the largest of all leukocytes. They are part of the innate immune system of vertebrates including all mammals (humans included), birds, reptiles, and fish. They are amoeboid in shape, having clear cytoplasm. Monocytes have bean-shaped nuclei that are unilobar, which makes them one of the types of mononuclear leukocytes (agranulocytes). Monocytes constitute 2% to 10% of all leukocytes in the human body. They play multiple roles in immune function. Such roles include:

(1) replenishing resident macrophages under normal states, and (2) in response to inflammation signals, monocytes can move quickly (approx. 8–12 hours) to sites of infection in the tissues and divide/differentiate into macrophages and dendritic cells to elicit an immune response. Half of them are stored in the spleen (except in people who have undergone splenectomy). Monocytes are usually identified in stained smears by their large kidney-shaped or notched nucleus. These change into macrophages after entering into the tissue spaces.

HLA-DRlowS100Ahigh monocytes, also known as non-classical monocytes or pro-inflammatory monocytes, are a specific subset of immune cells within the monocyte population. Monocytes are a type of white blood cell that plays a crucial role in the immune response and are involved in both innate and adaptive immunity.

The HLA-DR (human leukocyte antigen-DR) molecule is an essential component of the major histocompatibility complex class II (MHC-II) on the surface of antigen-presenting cells, including monocytes. HLA-DR is responsible for presenting antigens to T cells and initiating specific immune responses.

However, in certain conditions or diseases, a subset of monocytes can exhibit decreased expression of HLA-DR (HLA-DRlow) and increased expression of S100A proteins (S100Ahigh), particularly S100A8 and S100A9. S100A proteins are calcium-binding proteins associated with inflammation and immune regulation.

The HLA-DRlowS100Ahigh monocyte subset is characterized by a pro-inflammatory phenotype and functional properties. These cells are often found in inflammatory environments, such as in response to infection, autoimmune diseases, chronic inflammation, or tissue injury. They have been implicated in the pathogenesis of several inflammatory disorders, including sepsis, rheumatoid arthritis, systemic lupus erythematosus, and inflammatory bowel disease.

HLA-DRlowS100Ahigh monocytes are known to exhibit reduced antigen-presenting capacity and impaired T cell activation compared to classical monocytes with higher HLA-DR expression. They also produce higher levels of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and IL-6, contributing to the amplification and perpetuation of inflammatory responses.

The presence of HLA-DRlowS100Ahigh monocytes can serve as a biomarker of immune dysregulation and disease severity in certain conditions. Therapeutic interventions targeting these monocytes or their pro-inflammatory properties are being explored as potential strategies to modulate immune responses and mitigate inflammation-associated diseases.

It's important to note that research in this field is ongoing, and the understanding of HLA-DRlowS100Ahigh monocytes and their roles in different diseases is evolving. Further studies are needed to elucidate the precise mechanisms by which these monocytes contribute to immune dysregulation and their potential as therapeutic targets.

HLA-DRlowS100Ahigh monocytes correlated with immunosuppressive state upon septic challenge, inhibition of which can markedly mitigate sepsis-induced immune depression, thereby providing a novel therapeutic strategy for the management of sepsis 1)

Yao RQ, Zhao PY, Li ZX, Liu YY, Zheng LY, Duan Y, Wang L, Yang RL, Kang HJ, Hao JW, Li JY, Dong N, Wu Y, Du XH, Zhu F, Ren C, Wu GS, Xia ZF, Yao YM. Single-cell transcriptome profiling of sepsis identifies HLA-DRlowS100Ahigh monocytes with immunosuppressive function. Mil Med Res. 2023 Jun 19;10(1):27. doi: 10.1186/s40779-023-00462-y. PMID: 37337301.
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