Treatment of inflammatory bowel disease by chemokine receptor-targeted leukapheresis

Chemokine receptor expression on monocytes from healthy individuals

“…This chemokine-chemokine receptor interaction was utilized for therapeutic use thru manufacturing of a selective leukapheresis column containing an immobilized CCL25 with purpose to bind and remove CCR9-expressing cells from the circulation. A reported case study on one patient with ulcerative colitis treated with the chemokine receptor targeted leukapheresis demonstrated that CCR9-expressing monocytes were removed, and the patient was clinically in remission as demonstrated by sigmoideoscopy [7]. Here we demonstrated that the TNF-α producing pro-inflammatory HLA-DR hi monocytes is the subset with highest expression of CCR9.…”

“…For this, we have established normal reference values for chemokine receptor expression of 20 chemokine receptors on three monocyte subsets; classical (CD14 + CD16 − ), non-classical (CD14 + CD16 + ) and CD14 + HLA-DR hi Clinical Immunology 161 (2015) 348-353 monocytes from 20 healthy controls using multicolor flow cytometry. This will be particularly useful for exploring the pathological role of various aspects of chemokine-chemokine receptor interactions in IMIDs and inhibition of chemokine signaling or selective removal of migrating cells, which are shown to be new treatment strategies [7][8][9].…”

Chemokines in homeostasis and diseases

“…Chemokines and their GPCRs are associated with an extraordinary array of pathological conditions [52][53][54][55] (Table 5), including autoimmune disorders 8,[56][57][58][59][60][61] (for example, psoriasis, rheumatoid arthritis and multiple sclerosis); pulmonary diseases [62][63][64][65] (for example, asthma and chronic obstructive pulmonary disease); transplant rejection 70,71 ; metabolic and vascular diseases [66][67][68][69]78 (for example, obesity, diabetes and atherosclerosis; as well as infectious diseases [72][73][74][75][76][77] (for example, HIV, sepsis and inflammatory bowel disease). The active participation of chemokines and GPCRs in disease progression makes these molecules the most prominent targets for drug development.…”

CD69 Is the Crucial Regulator of Intestinal Inflammation: A New Target Molecule for IBD Treatment?

“…The blocking agents of CCR9, specific intestinal homing marker, could be beneficial for IBD patients, too. Recent study showed that removal of CCR9 + cells by leukapheresis was efficient in IBD treatment, but more extensive studies on this are needed [ 133 ].…”