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Updated: Aug 23, 2026
Induction of Murine Intestinal Inflammation by Adoptive Transfer of Effector CD4+CD45RBhigh T Cells into Immunodeficient Mice
Published on: April 21, 2015
Simultaneous deficiency in CD28 and STAT6 results in chronic ectoparasite-induced inflammatory skin disease
Qian Liu1, Cristin Arseculeratne, Zhugong Liu
1Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd., Bethesda, MD 20814, USA.
Abstract:
A mouse lacking CD28, a T-cell costimulatory molecule, and STAT6, a transcription factor that mediates interleukin-4 (IL-4) signaling, was developed from parental CD28- and STAT6-deficient mice. STAT6/CD28(-/-) BALB/c mice that were 8 weeks old had a normal phenotype, and IL-4 production was induced following infection with nematode parasites. Unexpectedly, when they were between 4 and 8 months old, all mice examined spontaneously developed severe chronic dermatitis associated with pronounced numbers of Demodex ectoparasites. In addition, pronounced CD4 and CD8 T-cell infiltrates in the dermis and subcutaneous fat, increased serum immunoglobulin G2a levels, and lymphadenopathy associated with increased gamma interferon and IL-12 expression were observed. Single-knockout siblings lacking either CD28 or STAT6 had a phenotype similar to that of BALB/c wild-type controls. To distinguish whether the ectoparasite Demodex or the Th1 immunity was the proximal cause of the inflammatory skin disease, STAT6/CD28(-/-) mice were treated with a miticide that eliminated the ectoparasites. This treatment markedly reduced the severity of the dermatitis and the associated lymphoid infiltrates. These findings suggest that ubiquitous ectoparasites, which are generally considered to be commensal, may contribute to disease when specific molecules required for an effective Th2 response are blocked.
Insights
Mice lacking key immune signaling molecules (CD28 and STAT6) developed severe dermatitis linked to Demodex mites. Eliminating mites reduced skin inflammation, suggesting parasites can trigger disease when Th2 responses are impaired.
Area of Science:
- Immunology
- Dermatology
- Microbiology
Background:
- CD28 is a T-cell costimulatory molecule.
- STAT6 mediates interleukin-4 (IL-4) signaling.
- A double-knockout mouse model lacking both CD28 and STAT6 was created.
Purpose of the Study:
- To investigate the phenotype of mice lacking both CD28 and STAT6.
- To determine the cause of spontaneous dermatitis in these mice.
- To explore the role of ectoparasites and Th1 immunity in skin inflammation.
Main Methods:
- Generation of STAT6/CD28(-/-) BALB/c mice.
- Phenotypic analysis and assessment of IL-4 production.
- Induction of nematode parasite infection.
- Treatment of mice with a miticide to eliminate Demodex ectoparasites.
Main Results:
- STAT6/CD28(-/-) mice developed spontaneous severe chronic dermatitis with Demodex infestation.
- Dermatitis was associated with CD4/CD8 T-cell infiltrates, increased IgG2a, lymphadenopathy, and Th1 cytokine expression (IFN-γ, IL-12).
- Miticide treatment significantly reduced dermatitis severity and lymphoid infiltrates, implicating Demodex as a trigger.
Conclusions:
- Blocking Th2 response pathways (via CD28 and STAT6 deficiency) can lead to severe dermatitis in the presence of normally commensal ectoparasites.
- Ubiquitous ectoparasites may contribute to inflammatory skin disease when immune responses are dysregulated.
- This study highlights the complex interplay between host immunity and microbial communities in skin health.
