Circulating integrin alpha4/beta7+ lymphocytes targeted by vedolizumab have a pro-inflammatory phenotype
| Autor: | Jane H. Buckner, Donna M. Shows, Katherine Schwedhelm, Janice Chen, Jerill Thorpe, Mariko Kita, James D. Lord, S. Alice Long |
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| Rok vydání: | 2018 |
| Předmět: |
Adult
Male Receptors CXCR5 0301 basic medicine Integrins Regulatory T cell medicine.medical_treatment Immunology chemical and pharmacologic phenomena Biology Antibodies Monoclonal Humanized T-Lymphocytes Regulatory Article Vedolizumab Immune tolerance Ikaros Transcription Factor 03 medical and health sciences Th2 Cells Immune system Gastrointestinal Agents Intestinal mucosa Immune Tolerance medicine Humans Immunology and Allergy Effector FOXP3 Forkhead Transcription Factors Middle Aged Th1 Cells Inflammatory Bowel Diseases Intestines 030104 developmental biology Cytokine medicine.anatomical_structure Blood Circulation Cytokines Female Inflammation Mediators medicine.drug |
| Zdroj: | Clinical Immunology. 193:24-32 |
| ISSN: | 1521-6616 |
| Popis: | Integrin alpha4/beta7 on circulating lymphocytes identifies them as gut-tropic, and can be targeted by the humanized antibody vedolizumab to treat inflammatory bowel disease (IBD). We found lymphocytes expressing alpha4/beta7 were significantly more responsive to the pro-inflammatory cytokines IL-6, IL-7, and IL-21, and less responsive to the regulatory T cell (Treg)-supporting cytokine IL-2. Alpha4/beta7 was expressed by a smaller percent of FOXP3 + Helios+ thymically-derived Tregs (tTregs) than FOXP3 + Helios- peripherally-derived Tregs (pTregs) or FOXP3- effector T cells. Integrin alpha4/beta7+ CD4 T cells were also rare among cells expressing the Th2 marker CRTh2, but enriched in cells bearing the circulating T follicular helper cell marker CXCR5. Thus the effect of this anti-integrin therapy on the mucosal immune system may be more qualitative than quantitative, and selectively replace pro-inflammatory effector cells with Tregs and Th2 cells to facilitate immune tolerance in the mucosa without globally depleting lymphocytes from the intestinal mucosa. |
| Databáze: | OpenAIRE |
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