Itgax, also known as CD11c, encodes integrin subunit alpha X. Integrins are cell-surface adhesion molecules involved in cell-cell and cell-extracellular matrix interactions. Itgax is associated with immune cell functions, playing a role in processes like cell adhesion, migration, and phagocytosis [3]. It is expressed in various immune cells such as macrophages, dendritic cells, and subsets of B cells, and is thus important in the immune response and in maintaining immune homeostasis. Genetic models, especially KO/CKO mouse models, can be valuable in studying its function in vivo.

In the context of age-associated B cells, the transcription factor ZEB2 targets Itgax, promoting age-associated B cell differentiation, which is crucial in the pathogenesis of lupus [1]. In rheumatoid arthritis, ITGAX+TBX21+ autoimmune-associated B cells are expanded in synovia, suggesting a role in the disease's pathogenesis [2]. In atherosclerosis, ITGAX is upregulated in atherosclerotic tissues, and its interaction with PAX5 affects the proliferation and inflammation of human vascular smooth muscle cells through the TNF-α signaling pathway [4]. In gastric cancer, ITGAX promotes cancer progression via the epithelial-mesenchymal transition pathway, and in melanoma, SERPINB8 and furin regulate ITGAX expression, which significantly impacts the proliferation and invasion of melanoma cells [5,6].

In summary, Itgax plays essential roles in immune-related biological processes and is implicated in multiple disease conditions, including lupus, rheumatoid arthritis, atherosclerosis, gastric cancer, and melanoma. Studies using KO/CKO mouse models could potentially further elucidate its functions in these disease areas, providing more insights into disease mechanisms and potential therapeutic targets.

References:

1. Dai, Dai, Gu, Shuangshuang, Han, Xiaxia, Vinuesa, Carola G, Shen, Nan. 2024. The transcription factor ZEB2 drives the formation of age-associated B cells. In Science (New York, N.Y.), 383, 413-421. doi:10.1126/science.adf8531. https://pubmed.ncbi.nlm.nih.gov/38271512/

2. Zhang, Fan, Wei, Kevin, Slowikowski, Kamil, Brenner, Michael B, Raychaudhuri, Soumya. 2019. Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry. In Nature immunology, 20, 928-942. doi:10.1038/s41590-019-0378-1. https://pubmed.ncbi.nlm.nih.gov/31061532/

3. Cai, Wei, Hu, Mengyan, Li, Chunyi, Lu, Yan, Lu, Zhengqi. 2022. FOXP3+ macrophage represses acute ischemic stroke-induced neural inflammation. In Autophagy, 19, 1144-1163. doi:10.1080/15548627.2022.2116833. https://pubmed.ncbi.nlm.nih.gov/36170234/

4. Wang, Xiangkui, Guan, Zeyu, Tang, Wenbo, Wang, Wei, Gao, Yong. 2023. PAX5/ITGAX Contributed to the Progression of Atherosclerosis by Regulation of B Differentiation via TNF-α Signaling Pathway. In DNA and cell biology, 42, 97-104. doi:10.1089/dna.2022.0461. https://pubmed.ncbi.nlm.nih.gov/36730754/

5. Hu, Jiali, Cao, Jing, Huang, Shanshan, Chen, Yang. 2025. ITGAX promotes gastric cancer progression via epithelial-mesenchymal transition pathway. In Frontiers in pharmacology, 15, 1536478. doi:10.3389/fphar.2024.1536478. https://pubmed.ncbi.nlm.nih.gov/39845786/

6. Ni, Li, Li, Pin, Li, Mingming, Huang, Shuhong, Dang, Ningning. 2022. SERPINB8 and furin regulate ITGAX expression and affect the proliferation and invasion of melanoma cells. In Experimental dermatology, 32, 24-29. doi:10.1111/exd.14677. https://pubmed.ncbi.nlm.nih.gov/36134483/