Expression of CD45 in non-hematopoietic cells: implications in regenerative medicine and disease management

Abstract

CD45 plays a crucial role in the regulation of hematopoiesis. However, a comprehensive understanding of its role in non-hematopoietic cells is lacking. Several tissue precursors express CD45, indicating its crucial role in tissue regeneration. These precursors would fall prey to the recent therapies involving CD45 as a target. CD45⁺ double-positive tumor cells contribute to cancer progression, but whether CD45 is involved in the process needs to be investigated. Recently, we showed that aging induces CD45 expression in mesenchymal stromal cells and affects their differentiation potential. In this review, we, for the first time, unravel the important implications of the expression of CD45 in non-hematopoietic cells and provide novel insights into its potential therapeutic target in regenerative medicine and disease management.

Article highlights

CD45: the critical modulator of hematopoiesis

• CD45 is abundantly found on almost all leukocytes and plays a critical role in the regulation of hematopoiesis. It has two intracellular phosphatase domains, one transmembrane and one extracellular domain. The intracellular domain has two phosphatase activity domains, and one domain has active intrinsic kinase activity. The C-terminal Src-kinase domain can phosphorylate the other domain.

Isoforms of CD45

• CD45 exhibits diverse isoforms resulting from alternative splicing during development. The hematopoietic lineage differentiation depends on the differential expression of various CD45 isoforms. This differential expression of CD45 isoforms serves as a diagnostic tool, influences immune function and causes autoimmune diseases.

CD45 in hematological disorders

• Dysregulated CD45 expression is associated with autoimmune diseases like multiple myeloma, SLE, etc. It could be one of the potential therapeutic targets for hematopoietic disorders and malignancies.

Role of CD45 in aging

• CD45 is also implicated in aging, though its role in aging per se needs to be identified. Oxidative stress to CD45 inactivates its phosphatase activity and alters TCR signaling, affecting immune functions. Aging alters the glycosylation pattern of CD45, leading to T-cell dysfunction. CD45 deficiency affects osteoclast formation. Expression of CD45 by aged MSCs leads to loss of their osteogenic differentiation potential and gain in adipogenic and osteoclastogenic differentiation potential.

CD45-positive cells as tissue precursors

• CD45 is expressed by various precursor cells, spanning organs such as the lung, pancreatic islets, liver, blood vessels and the nervous system. These dual-positive cells play an essential role in the endothelial-to-mesenchymal transition and chondrogenic differentiation, underscoring their therapeutic value in regenerative medicine.

Detrimental effects of CD45

• Implications in disease management: CD45⁺ fibrocytes arise from bone marrow and circulate in peripheral blood. They rapidly migrate to injured tissues and cause excessive fibrosis in autoimmune disorders like scleroderma. Likewise, after MI, CD45 expression in mitral valve endothelial cells causes EndMT and contributes to the fibrosis of the mitral valve. Circulating CD45⁺ DP tumor cells are valuable diagnostic indicators. They contribute to aggressive cancers with poor prognoses. CD45⁺ fibrocytes play a significant role in COPD pathogenesis. These reports indicate that CD45 is a potential therapeutic target in several diseases.

Conclusion

• The expression of CD45 in non-hematopoietic cells has significant implications in regenerative medicine and disease management. This aspect needs urgent attention to develop better regenerative therapies and therapeutics for managing various diseases.

Keywords: :

• CD45
• disease management
• double-positive circulating tumor cells
• End-MT
• regenerative medicine
• tissue precursors

Acknowledgments

The authors thank Symbiosis International University for intramural funding and Symbiosis Centre for Research and Innovations, Symbiosis International University.

Author contributions

M Das: concept, writing and editing of the manuscript; P Teli: writing and editing of the manuscript A Vaidyaa: reviewing & editing; VP Kale: conceptualization and designing, financial support, supervision, writing and editing of the manuscript, approval of the final draft.

Financial disclosure

Financial support was provided by Symbiosis Centre for Research and Innovations, Symbiosis International (Deemed University). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, stock ownership or options and expert testimony.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

Financial support was provided by Symbiosis Centre for Research and Innovations, Symbiosis International (Deemed University).