Type 1 diabetes (T1D) is characterized by autoimmune destruction of insulin-producing β cells in the pancreatic islets. Although autoreactive T cells have long been recognized as principal effectors, macrophages orchestrate nearly every phase of disease. In non-obese diabetic (NOD) mice and human pancreata, islet-resident and infiltrating monocyte-derived macrophages accumulate, polarize along context-dependent activation spectra, produce inflammatory mediators (e.g., IL-1β, TNF, IL-6), shape T- and B-cell responses, and directly participate in β-cell injury via inflammasome activation, oxidative burst, and phagocytosis. Conversely, macrophages can also adopt regulatory or reparative phenotypes that limit collateral damage and support β-cell survival.

Creative Biolabs provides experimental platforms to interrogate macrophage functions, mechanisms, and interventions across in vitro models.

The Roles of Macrophages in T1D

Studies have indicated the possible roles of macrophages in T1D. The initiator events occur in still functional prediabetic β-cells when pathways promoting islet inflammation are triggered. The initiation of insulitis in T1D is driven by initiator stimuli, such as damage-associated and pathogen-associated molecular patterns or cytokines (interleukin 1β (IL-1β) and interferon γ (IFNγ)) binding to specific receptors on the surface of β-cells and inducing endoplasmic reticulum stress and nuclear factor kappa-B (NFκB)- and signal transducer and activator of transcription 1 (STAT1)-dependent pathways. This leads to the activation of apoptotic pathways and the expression of chemokines. Chemokines attract pro-inflammatory monocytes from the circulation that differentiate into islet macrophages which, in turn, release cytokines targeting β-cells. Apoptotic bodies and TLR ligands may also induce pro-inflammatory polarisation of islet resident macrophages. Pro-inflammatory macrophages mediate T-cell recruitment via antigen presentation and finally phagocytose damaged β-cells.

Fig.1 β-cell–macrophage communication during insulitis in T1Ds.¹

Macrophage Function and β-cell

The role of macrophages is vital for the forming of the mass of insulin-secreting cells but is inessential for the development of glucagon secreting cells. Due to their role in the processing and presentation of β-cell antigens to autoreactive T cells, M1 macrophages are the principal macrophage subtype of focus in T1D. M1 macrophages contribute NF-kB and STAT1 activation results in caspase 1/3/9/12 activation and subsequent β-cell death. It was reported that M2 islet macrophages can secrete insulin-like growth factor 1 (IGF-1) after β-cell death, prompting β-cell proliferation and promoting their viability. M2 macrophages facilitate β-cell protection and regeneration through secretion of several growth factors (i.e., transforming growth factorβ (TGFβ), epidermal growth factor (EGF), IGF-1) in concert with endothelial cell-derived growth factors (i.e., hepatocyte growth factor (HGF), fibroblast growth factor(FGF), IGF-1).

Macrophage Lineages in the Pancreas

• Islet-Resident Macrophages (TRMs): Predominantly yolk sac/fetal liver derived with self-renewal capacity; partially replaced by monocytes under inflammatory stress.
• Monocyte-Derived Macrophages (mo-Macs): CCR2-dependent egress of Ly6C^hi (human CD14^++) monocytes from bone marrow and spleen; chemokines CCL2/7/8/12 guide islet homing.
• Dendritic Cell–Macrophage Continuum: CD11c^+ macrophages share features with conventional DCs (cDC2-like) in islets; plasticity complicates strict lineage demarcation but broadens antigen-presenting capacity.

How Creative Biolabs Can Help

Our platform is built on a deep expertise in macrophage biology and islet immunology, providing our clients with the critical tools and models needed to develop next-generation T1D therapeutics.

Macrophage Polarization Assays

• Induction: IFN-γ/LPS (pro-inflammatory), IL-4/IL-13 (regulatory), IL-10/TGF-β (tolerogenic), GM-CSF/M-CSF differentiation.
• Readouts: Flow cytometry panels (CD80/CD86, MHC-II, CD206, MerTK, PD-L1), qPCR/ELISA multiplex, metabolic flux, NO/ROS, cytokine profiling.

Macrophage–β Cell / Islet Co-Cultures

• Primary human islets or β-cell lines (e.g., EndoC-βH) with autologous or allogeneic monocyte-derived macrophages.
• Endpoints: β-cell viability, insulin secretion, ER stress markers, single-cell transcriptomes, spatial IF.

Macrophage Functional Assays

• Phagocytosis: Quantifying uptake of debris, zymosan, or apoptotic cells.
• Migration/Chemotaxis: Using microfluidic devices to assess cell migration towards key chemokines (CCL2, CXCL10).
• Cytokine & Chemokine Profiling: Multiplex analysis of secreted products (IL-1β, TNF-α, IL-10, CCL2) from cultured macrophages or islet supernatants.

High-Content Analysis

• Multiplex Immunofluorescence (mIF) / IHC: We provide spatial profiling of the insulitic lesion, co-localizing macrophage markers (e.g., CD68, iNOS, CD206) with T-cells (CD4, CD8), β-cells (Insulin), and structural components.
• High-Parameter Flow Cytometry: We offer deep immune-phenotyping panels (30+ markers) to dissect the heterogeneity of islet-infiltrating myeloid cells, identifying novel subsets.

Omics Solutions

• Spatial Transcriptomics: Overlaying gene expression maps onto tissue architecture to understand how macrophage function is dictated by its precise location within the islet.
• Metabolomics: Characterizing the metabolic profile of macrophage populations to identify new therapeutic targets.

We provide end-to-end solutions, from target discovery to preclinical validation, all centered on macrophage biology.

Workflow

Therapeutic Targeting of Macrophages for T1D Intervention

The central role of macrophages as instigators, presenters, and effectors in T1D makes them an exceptionally attractive, albeit complex, therapeutic target.

Strategies of Targeting Macrophages in T1D

Preliminary treatments for T1D have focused on depleting or repolarizing macrophages. 1) Targeted depletion of macrophages by clodronate liposomes was shown to abolish diabetes in non-obese diabetic mice, although inflammation persisted. 2) Anti-inflammatory drugs such as dexamethasone, promote M2 phenotype by reprogramming macrophages. Efforts to suppress M1 phenotypes through the adoptive transfer of M2 macrophages reduced T1D onset in non-obese diabetic mice and reduced hyperglycemia, kidney injury, and insulitis in vitro. 3) Inhibiting the inflammatory effector functions of macrophages by monoclonal antibodies against colony-stimulating factor (CSF-1) receptors reduced diabetes incidence and promoted a regulatory pathway for autoimmune progression. To limit macrophage-derived tumor necrosis factor (TNFα) by TNF-α blockades have demonstrated clinical efficacy, but they remain controversial because of the disturbance of glycemic control. Nonetheless, targeting macrophages to treat T1D is at the infancy stage, demonstrating a wide treatment gap.

Macrophages play an important role in T1D. Identification of macrophage subtypes and their secreted factors might ultimately translate into novel therapeutic strategies for T1D. Based on an advanced Macrophage Therapeutics Development platform, Creative Biolab has been committed to the field of macrophage development. With professional and abundant experience over the decade, we provide a series of comprehensive services to meet our clients' demands.

Advancing Macrophage-Based T1D Research

To support the global research community in the field of autoimmunity, Creative Biolabs has developed a comprehensive and highly customizable suite of macrophage research services. Our platform combines state-of-the-art technologies with a team of senior immunologists to provide you with reliable, reproducible data.

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Q & A

Q: What molecular signals drive macrophage polarization in diabetic islets?

A: Key cues include IFN-γ, TNF, IL-1β, and TLR ligands for inflammatory activation, versus IL-4, IL-10, and TGF-β for anti-inflammatory programming. Metabolic intermediates such as succinate, itaconate, and citrate further fine-tune macrophage transcriptional programs.

Q: What biomarkers indicate macrophage activation in T1D research?

A: Common markers include CD68, CD80, CD86, MHC-II, CD206, CD163, and TREM2. Circulating soluble markers such as sCD163, IL-1β, IL-18, CXCL10, and TNF are measurable in plasma and correlate with disease activity in research cohorts.

Q: Can macrophages be used therapeutically in T1D research models?

A: In preclinical settings, tolerogenic macrophages (tol-Macs)—generated ex vivo with IL-10, TGF-β, or metabolic reprogramming—can suppress autoreactive T cells and delay diabetes onset in NOD mice. Creative Biolabs supports customized generation and functional testing of such macrophage populations.

Q: What support can Creative Biolabs provide for custom T1D macrophage projects?

A: Our team designs end-to-end research solutions—from macrophage isolation, differentiation, and polarization to high-content screening, single-cell analytics, and preclinical validation. We deliver data-driven insights tailored to your scientific goals, enabling faster, evidence-based decision-making in macrophage-targeted T1D research.

Creative Biolabs provides modular, human-relevant platforms to accelerate T1D research timelines. Tell us your hypothesis and desired endpoints—we'll propose a fit-for-purpose study plan, budget, and timeline.

Contact Creative Biolabs to discuss your T1D macrophage project.

Reference

1. Cosentino, Cristina, and Romano Regazzi. "Crosstalk between macrophages and pancreatic β-cells in islet development, homeostasis and disease." International Journal of Molecular Sciences 22.4 (2021): 1765. Distributed under Open Access license CC BY 4.0, without modification. https://doi.org/10.3390/ijms22041765