MDC Human serves as a chemotactic ligand for CCR4, a receptor expressed on activated T lymphocytes, monocytes, dendritic cells, and natural killer (NK) cells . Its primary functions include:
Immune Cell Recruitment: Guides chronically activated T lymphocytes, monocytes, dendritic cells, and IL-2-activated NK cells to inflammatory sites .
Tissue-Specific Activity: Minimal or no attraction for neutrophils, eosinophils, or resting T lymphocytes .
Immunoregulation: Facilitates trafficking of activated T cells and modulates immune responses in inflammatory environments .
Key Receptor Interaction:
MDC Human expression is tightly regulated and cell-type specific:
Northern blot analyses confirm that MDC mRNA is absent in monocytes, NK cells, and non-hematopoietic cell lines but highly expressed in thymus, lung, and spleen .
MDC was first isolated from a human macrophage cDNA library and distinguished by its unique sequence (<35% identity to other CC chemokines) . Recombinant MDC expressed in Chinese hamster ovary cells showed:
Chemotactic Dose-Response: Maximal migration of dendritic cells and NK cells at 1 ng/ml .
Molecular Mass Verification: Confirmed as 8,081 Da via mass spectrometry .
MDC/CCL22 is implicated in:
Chronic Inflammation: Elevated in diseases like asthma and inflammatory bowel disease .
Cancer Immunology: Role in tumor microenvironment modulation via dendritic cell recruitment .
Feature | His-Tagged | Untagged |
---|---|---|
Amino Acids | 90 (25–93 aa) | 69 (core) |
Molecular Mass | 10.3 kDa | 8.1 kDa |
Formulation | PBS + 10% glycerol | Lyophilized powder |
Cell Type | Maximum Response (ng/ml) | Key Observations |
---|---|---|
Dendritic Cells | 1 | Dose-dependent migration |
IL-2-Activated NK Cells | 1 | Requires prior IL-2 activation |
Monocytes | 100 | Lower sensitivity compared to dendritic cells |
The MDC research approval process follows a two-step methodology that ensures ethical standards while maintaining institutional priorities. First, MDC's Institutional Review Board (IRB) reviews human subjects research proposals to ensure: (1) the rights and welfare of human subjects are protected; (2) risks have been minimized; (3) potential benefits have been identified; (4) all human subjects volunteer after receiving legally effective informed consent; and (5) research is conducted ethically and in compliance with MDC standards . Second, once approved by the IRB, the proposal is routed to the College Academic and Student Support Council Research and Testing Subcommittee (CASSC R&T), which evaluates alignment with strategic priorities, institutional values, and potential burden on MDC resources . Researchers may not begin soliciting participants or collecting data until both approvals are secured .
Research applications must include documentation that Principal and Co-Investigators have successfully completed training in the responsible conduct of research . MDC provides free access to the "Social & Behavioral Research Basic Course" for employees and students who need certification for coursework, grant work, or assignments related to the CASSC Research and Testing Committee, Data Liaisons, or IRB . The registration process requires using an MDC email address. Additionally, the Office for Human Research Protections (OHRP) offers various free online trainings based on the principles of the Belmont Report and the requirements of the revised Common Rule (2018 Requirements) .
Researchers should allocate 6-8 weeks for the complete application review process . Data collection cannot commence until researchers receive formal notification that their application has been approved by both MDC's IRB and the CASSC Research & Testing Committee . The review schedule follows specific deadlines throughout the academic year, with approximately two weeks between the IRB review and the CASSC committee review, followed by notification approximately two weeks after that review .
Despite revisions to Common Rule 45 CFR § 46.103 that removed requirements for IRBs to review entire grant applications, Principal Investigators remain responsible for ensuring consistency between IRB submissions and grant proposals submitted to federal agencies . Any federally-funded study or research involving human subjects receiving federal funding requires IRB approval . Some exemptions may apply under 45 CFR § 46.101 and 45 CFR § 46.104, but researchers should anticipate IRB review requirements when pursuing grant funding since Miami Dade College is largely a recipient of federal funding . This methodological framework ensures regulatory compliance while protecting research participants.
MDC implements a structured approach to risk-benefit assessment through its IRB review process. Risks to subjects must be reasonable in relation to anticipated benefits (if any), to subjects themselves, and to the importance of knowledge reasonably expected to result . The IRB evaluates whether adequate provisions exist for all facilities, procedures, and professional attention necessary for subject protection . This methodological approach requires researchers to demonstrate that potential benefits justify any risks through systematic analysis, ensuring ethical research conduct while protecting participant welfare.
MDC imposes methodological requirements for recruiting subject populations representative of the population base in terms of gender and minority representation unless scientifically justified otherwise . This approach ensures research findings have greater generalizability across diverse populations while avoiding selection biases that could compromise research validity. Researchers must describe their recruitment strategies and justify any limitations in population diversity as part of their IRB application, demonstrating how their methodology addresses representation concerns.
Human Macrophage-derived Chemokine (MDC) is a novel chemokine isolated through random sequencing of cDNA clones from human monocyte-derived macrophages . MDC represents a unique member of the CC chemokine family, sharing less than 35% identity with previously known chemokines while maintaining the characteristic four-cysteine motif and other highly conserved residues . The protein appears specifically synthesized by cells of the macrophage lineage and plays fundamental roles in the function of dendritic cells, natural killer cells, and monocytes . MDC has a molecular weight of 8,081 dalton, verified through mass spectrophotometry .
MDC shows a distinct expression pattern limited primarily to cells of the macrophage lineage. Northern analyses indicate high expression in macrophages and monocyte-derived dendritic cells, but not in monocytes, natural killer cells, or several cell lines of epithelial, endothelial, or fibroblast origin . At the tissue level, high expression appears in normal thymus with lower expression detected in lung and spleen . This restricted expression pattern suggests specialized immunological functions in specific tissues and cell types involved in adaptive and innate immunity.
Recombinant MDC has been validated through rigorous biochemical and functional assays. After expression in Chinese hamster ovary cells and purification by heparin-Sepharose chromatography, the purified protein was confirmed through NH2-terminal sequencing and mass spectrophotometry . In microchamber migration assays, monocyte-derived dendritic cells and IL-2–activated natural killer cells demonstrated dose-dependent migration toward MDC with maximal chemotactic response at 1 ng/ml . Freshly isolated monocytes also migrated toward MDC but required a higher concentration (100 ng/ml) for peak response . These methodological approaches definitively established MDC's function as a chemotactic factor with differential potency across immune cell subtypes.
MDC expression regulation has been systematically studied using the HL60 cell line differentiation model. When treated with PMA (50 ng/ml), which induces differentiation toward the macrophage lineage, HL60 cells show clear MDC expression after 3 days, though at lower levels than primary monocyte-derived macrophages . Conversely, no MDC expression appears after 1 day of PMA treatment, in untreated cells, or in granulocytic cells generated by DMSO treatment . This experimental approach demonstrates that MDC expression is specifically linked to macrophage differentiation pathways rather than granulocytic lineage development.
The following table outlines the current application cycle deadlines and review timeframes for conducting research at Miami Dade College for 2025:
Research Application Deadline | MDC IRB Review | CASSC R&T Committee Review | Notification to Applicants |
---|---|---|---|
Dec 27, 2024 | Jan 13, 2025 | Jan 27, 2025 | By Feb 10, 2025 |
Jan 24, 2025 | Feb 10, 2025 | Feb 24, 2025 | By Mar 10, 2025 |
Mar 7, 2025 | Mar 24, 2025 | Apr 7, 2025 | By Apr 21, 2025 |
Apr 11, 2025 | Apr 28, 2025 | May 12, 2025 | By May 26, 2025 |
May 30, 2025 | Jun 16, 2025 | Jun 30, 2025 | By Jul 14, 2025 |
Jun 27, 2025 | Jul 14, 2025 | Jul 28, 2025 | By Aug 11, 2025 |
Jul 25, 2025 | Aug 11, 2025 | Aug 25, 2025 | By Sep 8, 2025 |
Aug 29, 2025 | Sep 15, 2025 | Sep 29, 2025 | By Oct 13, 2025 |
Sep 26, 2025 | Oct 13, 2025 | Oct 27, 2025 | By Nov 10, 2025 |
Nov 7, 2025 | Nov 24, 2025 | Dec 8, 2025 | By Dec 22, 2025 |
Researchers must submit applications by the specified deadlines to ensure timely review and approval . This structured timeline allows for methodical planning of research activities while ensuring compliance with institutional protocols.
Macrophage-Derived Chemokine (MDC), also known as CCL22, is a member of the C-C chemokine family. Chemokines are small cytokines or signaling proteins secreted by cells, and they play a crucial role in immune responses by directing the movement of circulating leukocytes to sites of inflammation or injury. CCL22 is primarily produced by dendritic cells and macrophages and is involved in the recruitment of T cells, particularly regulatory T cells (Tregs), to sites of inflammation .
The gene encoding CCL22 is located on chromosome 16 in humans. This gene is part of a cluster of chemokine genes, which includes other members such as CX3CL1 and CCL17 . The protein structure of CCL22 consists of a typical chemokine fold, which includes a three-stranded β-sheet and a C-terminal α-helix. This structure is essential for its interaction with chemokine receptors on target cells.
CCL22 exerts its effects by binding to the chemokine receptor CCR4, which is expressed on various immune cells, including T cells, natural killer (NK) cells, and dendritic cells . The primary function of CCL22 is to mediate chemotaxis, the directed movement of cells towards higher concentrations of the chemokine. This process is vital for the immune system’s ability to respond to infections and other inflammatory stimuli.
CCL22 plays a significant role in the immune response by recruiting Tregs to sites of inflammation. Tregs are essential for maintaining immune tolerance and preventing excessive immune reactions that can lead to tissue damage. By attracting Tregs, CCL22 helps modulate the immune response and maintain a balance between effective pathogen clearance and limiting collateral damage to host tissues .
The expression of CCL22 has been implicated in various diseases, including cancer, autoimmune disorders, and infectious diseases. For instance, elevated levels of CCL22 have been observed in certain types of cancer, where it may contribute to the recruitment of Tregs to the tumor microenvironment, thereby promoting immune evasion by the tumor . Conversely, reduced levels of CCL22 have been noted in some autoimmune diseases, suggesting a potential role in disease pathogenesis.
Given its role in immune regulation, CCL22 is a target of interest for therapeutic interventions. Modulating CCL22 levels or blocking its interaction with CCR4 could potentially enhance anti-tumor immunity or ameliorate autoimmune conditions. Ongoing research aims to better understand the mechanisms by which CCL22 influences immune responses and to develop strategies for targeting this chemokine in various diseases .