INCREASED INFLAMMATORY CELL PROFILE TOGETHER WITH MERTK UP REGULATION AND T CELL-DERIVED PROTEIN S REDUCTION IN IBD PATIENTS

LICINA TESSONE; PAULA CHAVERO; SILVIA PERÉS WINGEYER; GABRIELA DE LARRAÑAGA; ALICIA SAMBUELLI; CARLA V. ROTHLIN; E. ANTONIO CARRERA SILVA; ANDREA E. ERRASTI

Mar del Plata

Congreso; Reunión Conjunta SAIC-SAI-SAFE 2016; 2016

SAIC-SAI-SAFE

&amp;amp;lt;!-- /* Font Definitions */@font-face{font-family:Arial;panose-1:2 11 6 4 2 2 2 2 2 4;mso-font-charset:0;mso-generic-font-family:auto;mso-font-pitch:variable;mso-font-signature:-536859905 -1073711037 9 0 511 0;}@font-face{font-family:"&amp;amp;#65325;&amp;amp;#65331; &amp;amp;#26126;&amp;amp;#26397;";mso-font-charset:78;mso-generic-font-family:auto;mso-font-pitch:variable;mso-font-signature:-536870145 1791491579 18 0 131231 0;}@font-face{font-family:"Cambria Math";panose-1:2 4 5 3 5 4 6 3 2 4;mso-font-charset:0;mso-generic-font-family:auto;mso-font-pitch:variable;mso-font-signature:-536870145 1107305727 0 0 415 0;}@font-face{font-family:Cambria;panose-1:2 4 5 3 5 4 6 3 2 4;mso-font-charset:0;mso-generic-font-family:auto;mso-font-pitch:variable;mso-font-signature:-536870145 1073743103 0 0 415 0;} /* Style Definitions */p.MsoNormal, li.MsoNormal, div.MsoNormal{mso-style-unhide:no;mso-style-qformat:yes;mso-style-parent:"";margin:0in;margin-bottom:.0001pt;mso-pagination:widow-orphan;font-size:12.0pt;font-family:Cambria;mso-ascii-font-family:Cambria;mso-ascii-theme-font:minor-latin;mso-fareast-font-family:"&amp;amp;#65325;&amp;amp;#65331; &amp;amp;#26126;&amp;amp;#26397;";mso-fareast-theme-font:minor-fareast;mso-hansi-font-family:Cambria;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:"Times New Roman";mso-bidi-theme-font:minor-bidi;}.MsoChpDefault{mso-style-type:export-only;mso-default-props:yes;font-family:Cambria;mso-ascii-font-family:Cambria;mso-ascii-theme-font:minor-latin;mso-fareast-font-family:"&amp;amp;#65325;&amp;amp;#65331; &amp;amp;#26126;&amp;amp;#26397;";mso-fareast-theme-font:minor-fareast;mso-hansi-font-family:Cambria;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:"Times New Roman";mso-bidi-theme-font:minor-bidi;}@page WordSection1{size:8.5in 11.0in;margin:1.0in 1.25in 1.0in 1.25in;mso-header-margin:.5in;mso-footer-margin:.5in;mso-paper-source:0;}div.WordSection1{page:WordSection1;}--&amp;amp;gt;Background: Crohn?s disease (CD) and Ulcerative Colitis (UC) areInflammatory Bowel Diseases (IBD) characterized by chronic inflammation andtissue damage.  Protein S (PROS1), anagonist of TYRO3, AXL and MERTK (TAM) receptors, is expressed upon T cellactivation reducing dendritic cell activation. Genetic ablation of Axl and Mertkincreases the inflammatory signature and loss of tissue repair macrophagephenotype in a mouse model of IBD. Purpose:Our goal was to characterize the immune compartments, TAM receptors and PROS1expression in monocyte/macrophage and lymphocytes of IBD patients. Results: Blood mononuclear cells from33 IBD patients (16 CD/17 UC) classified as active disease (AD) or in remissionby CDAI and Mayo scores, and 35 healthy controls were analyzed by FACS. Increased% of CD14highCD11bhighCD11c+ monocytes were observedin active IBD (21.1 ± 2.2 N=20) vs remission (9.6 ± 1.0 N=13) and controls (8.7± 0.6 N=19) and positively correlated with the CDAI (r=0.67 p<0.01) or Mayoscores (r=0.82 p<0.001). Interestingly, we observed an increased % of CD11blowCD64+CD206-cells in active IBD (48.2 ± 9.7 N=9) vs remission (13.3 ± 4.2 N=12) andcontrols (7.2 ± 1.2 N=14). Although AXL is highly expressed in circulatingmonocytes, no differences between IBD vs controls were observed. However, we dodetect a significant up-regulation of MERTK comparing IBD vs controls(p<0.01). TYRO3 was differentially expressed in monocytes of only CD vs controls.In-vitro TCR stimulation with a-CD3/CD28 leads to a significant lower level ofPROS1 in CD4 T cells of active CD. Conclusions:Our results show a clear inflammatory cell profile with increased level ofcirculating monocytes and CD64+CD206- cells in active IBD.Interestingly, MERTK that is associated with tolerogenic responses wasconsistently up regulated in monocytes of active IBD. Moreover, CD4 T cellsshowed reduced levels of PROS1 after activation reflecting a more inflammatorymemory profile in IBD patients.